Abstract
The biological effects of somatostatin (SST) were first encountered unexpectedly in the late 1960s in two unrelated studies, one by Krulich et al. (1968) who reported on a growth hormone (GH)-releasing inhibitory substance from hypothalamic extracts, and the other, by Hellman and Lernmark (1969), on the presence of a potent insulin inhibitory factor from the extracts of pigeon pancreatic islets. However, the inhibitory substance was not officially identified until 1973 by Guillemin’s group (Brazeau et al. 1973). In both synthetic and naturally occurring forms, this tetradecapeptide, originally coined as somatotropin release-inhibitory factor (SRIF, SST-14) was shown by Brazeau et al. to be the substance controlling hypothalamic GH release. This single achievement not only pioneered SST research but was also duly recognized, as Guillemin shared the 1977 Nobel Prize in Medicine. The following years bequeathed an exponential increase in SST-related studies. It soon became clear that SST-synthesis was not restricted to the hypothalamus. Its production is widely distributed throughout the central nervous system (CNS), peripheral neurons, the gastrointestinal tract, and the pancreatic islets of Langerhans (Luft et al. 1974; Arimura et al. 1975; Dubois 1975; Hokfelt et al. 1975; Orci et al. 1975; Pelletier et al. 1975; Polak et al. 1975; Patel and Reichlin 1978). In fact, SST-like immunoreactivity can be found throughout various tissues of vertebrates and invertebrates, including the plant kingdom (Patel 1992; Tostivint et al. 2004). Given its broad anatomical distribution, it is no wonder that SST produces a wide spectrum of biological effects. Generally regarded as an inhibitory factor, SST can function either locally on neighboring cells or distantly through the circulation, to regulate such physiological processes as glandular secretion, neurotransmission, smooth muscle contractility, nutrient absorption, and cell division (Reichlin 1983a, b; Patel 1992, 1999; Patel et al. 2001; Barnett 2003).
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References
Abs R, Verhelst J, Maiter D et al (1998) Cabergoline in the treatment of acromegaly: a study in 64 patients. J Clin Endocrinol Metab 83:374–378
Aguila MC (1994) Growth hormone-releasing factor increases somatostatin release and mRNA levels in the rat periventricular nucleus via nitric oxide by activation of guanylate cyclase. Proc Natl Acad Sci USA 91:782–786
Aguila MC, Dees WL, Haensly WE et al (1991) Evidence that somatostatin is localized and synthesized in lymphoid organs. Proc Natl Acad Sci USA 88:11485–11489
Aguila MC, Rodriguez AM, Aguila-Mansilla HN et al (1996) Somatostatin antisense oligodeoxynucleotide-mediated stimulation of lymphocyte proliferation in culture. Endocrinology 137:1585–1590
Akopian A, Johnson J, Gabriel R et al (2000) Somatostatin modulates voltage-gated K(+) and Ca(2+) currents in rod and cone photoreceptors of the salamander retina. J Neurosci 20:929–936
Alberti KG, Christensen NJ, Christensen SE et al (1973) Inhibition of insulin secretion by somatostatin. Lancet 2:1299–1301
Albini A, Florio T, Giunciuglio D et al (1999) Somatostatin controls Kaposi’s sarcoma tumor growth through inhibition of angiogenesis. FASEB J 13:647–655
Alderton F, Fan TP, Humphrey PP (2001) Somatostatin receptor-mediated arachidonic acid mobilization: evidence for partial agonism of synthetic peptides. Br J Pharmacol 132:760–766
Altomare DA, Testa JR (2005) Perturbations of the AKT signaling pathway in human cancer. Oncogene 24:7455–7464
Amherdt M, Patel YC, Orci L (1989) Binding and internalization of somatostatin, insulin, and glucagon by cultured rat islet cells. J Clin Invest 84:412–417
Arena S, Pattarozzi A, Massa A et al (2007) An intracellular multi-effector complex mediates somatostatin receptor 1 activation of phospho-tyrosine phosphatase eta. Mol Endocrinol 21:229–246
Arimura A, Schally AV (1976) Increase in basal and thyrotropin-releasing hormone (TRH)-stimulated secretion of thyrotropin (TSH) by passive immunization with antiserum to somatostatin in rats. Endocrinology 98:1069–1072
Arimura A, Sato H, Dupont A et al (1975) Somatostatin: abundance of immunoreactive hormone in rat stomach and pancreas. Science 189:1007–1009
Bai M (2004) Dimerization of G-protein-coupled receptors: roles in signal transduction. Cell Signal 16:175–186
Ballian N, Brunicardi FC, Wang XP (2006) Somatostatin and its receptors in the development of the endocrine pancreas. Pancreas 33:1–12
Baragli A, Alturaihi H, Watt HL et al (2007) Heterooligomerization of human dopamine receptor 2 and somatostatin receptor 2 Co-immunoprecipitation and fluorescence resonance energy transfer analysis. Cell Signal 19:2304–2316
Barber DL, McGuire ME, Ganz MB (1989) Beta-adrenergic and somatostatin receptors regulate Na-H exchange independent of cAMP. J Biol Chem 264:21038–21042
Barinaga M, Bilezikjian LM, Vale WW et al (1985) Independent effects of growth hormone releasing factor on growth hormone release and gene transcription. Nature 314:279–281
Barkan AL, Dimaraki EV, Jessup SK et al (2003) Ghrelin secretion in humans is sexually dimorphic, suppressed by somatostatin, and not affected by the ambient growth hormone levels. J Clin Endocrinol Metab 88:2180–2184
Barnett P (2003) Somatostatin and somatostatin receptor physiology. Endocrine 20:255–264
Barrie R, Woltering EA, Hajarizadeh H et al (1993) Inhibition of angiogenesis by somatostatin and somatostatin-like compounds is structurally dependent. J Surg Res 55:446–450
Baskin DG, Ensinck JW (1984) Somatostatin in epithelial cells of intestinal mucosa is present primarily as somatostatin 28. Peptides 5:615–621
Bass RT, Buckwalter BL, Patel BP et al (1996) Identification and characterization of novel somatostatin antagonists. Mol Pharmacol 50:709–715
Bauer W, Briner U, Doepfner W et al (1982) SMS 201–995: a very potent and selective octapeptide analogue of somatostatin with prolonged action. Life Sci 31:1133–1140
Bayburt TH, Leitz AJ, Xie G et al (2007) Transducin activation by nanoscale lipid bilayers containing one and two rhodopsins. J Biol Chem 282:14875–14881
Bell JR, Young MR, Masterman SC et al (1999) A pilot study of naltrexone-accelerated detoxification in opioid dependence. Med J Aust 171:26–30
Benoit R, Ling N, Esch F (1987) A new prosomatostatin-derived peptide reveals a pattern for prohormone cleavage at monobasic sites. Science 238:1126–1129
Ben-Shlomo A, Wawrowsky KA, Proekt I et al (2005) Somatostatin receptor type 5 modulates somatostatin receptor type 2 regulation of adrenocorticotropin secretion. J Biol Chem 280:24011–24021
Benuck M, Marks N (1976) Differences in the degradation of hypothalamic releasing factors by rat and human serum. Life Sci 19:1271–1276
Berelowitz M, Firestone SL, Frohman LA (1981a) Effects of growth hormone excess and deficiency on hypothalamic somatostatin content and release and on tissue somatostatin distribution. Endocrinology 109:714–719
Berelowitz M, Szabo M, Frohman LA et al (1981b) Somatomedin-C mediates growth hormone negative feedback by effects on both the hypothalamus and the pituitary. Science 212:1279–1281
Berelowitz M, Dudlak D, Frohman LA (1982) Release of somatostatin-like immunoreactivity from incubated rat hypothalamus and cerebral cortex. Effects of glucose and glucoregulatory hormones. J Clin Invest 69:1293–1301
Berglund MM, Schober DA, Esterman MA et al (2003) Neuropeptide Y Y4 receptor homodimers dissociate upon agonist stimulation. J Pharmacol Exp Ther 307:1120–1126
Bersani M, Thim L, Baldissera FG et al (1989) Prosomatostatin 1–64 is a major product of somatostatin gene expression in pancreas and gut. J Biol Chem 264:10633–10636
Bevan JS (2005) Clinical review: The antitumoral effects of somatostatin analog therapy in acromegaly. J Clin Endocrinol Metab 90:1856–1863
Blum AM, Metwali A, Mathew RC et al (1992) Granuloma T lymphocytes in murine schistosomiasis mansoni have somatostatin receptors and respond to somatostatin with decreased IFN-gamma secretion. J Immunol 149:3621–3626
Boudin H, Sarret P, Mazella J et al (2000) Somatostatin-induced regulation of SST(2A) receptor expression and cellsurface availability in central neurons: role of receptor internalization. J Neurosci 20:5932–5939
Bousquet C, Delesque N, Lopez F et al (1998) sst2 somatostatin receptor mediates negative regulation of insulin receptor signaling through the tyrosine phosphatase SHP-1. J Biol Chem 273:7099–7106
Bousquet C, Puente E, Buscail L et al (2001) Antiproliferative effect of somatostatin and analogs. Chemotherapy 47(Suppl 2):30–39
Brazeau P, Vale W, Burgus R et al (1973) Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 179:77–79
Breitwieser GE (2004) G protein-coupled receptor oligomerization: implications for G protein activation and cell signaling. Circ Res 94:17–27
Bresson JL, Clavequin MC, Fellmann D et al (1984) Ontogeny of the neuroglandular system revealed with HPGRF 44 antibodies in human hypothalamus. Neuroendocrinology 39:68–73
Bruno JF, Xu Y, Song J et al (1993) Tissue distribution of somatostatin receptor subtype messenger ribonucleic acid in the rat. Endocrinology 133:2561–2567
Bruno JF, Xu Y, Berelowitz M (1994a) Somatostatin regulates somatostatin receptor subtype mRNA expression in GH3 cells. Biochem Biophys Res Commun 202:1738–1743
Bruno JF, Xu Y, Song J et al (1994b) Pituitary and hypothalamic somatostatin receptor subtype messenger ribonucleic acid expression in the food-deprived and diabetic rat. Endocrinology 135:1787–1792
Bruns C, Lewis I, Briner U et al (2002) SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol 146:707–716
Bugnon C, Fellmann D, Bloch B (1978) Immunocytochemical study of the ontogenesis of the hypothalamic somatostatin-containing neurons in the human fetus. Metabolism 27:1161–1165
Buscail L, Delesque N, Esteve JP et al (1994) Stimulation of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: mediation by human somatostatin receptor subtypes SSTR1 and SSTR2. Proc Natl Acad Sci USA 91:2315–2319
Buscail L, Esteve JP, Saint-Laurent N et al (1995) Inhibition of cell proliferation by the somatostatin analogue RC-160 is mediated by somatostatin receptor subtypes SSTR2 and SSTR5 through different mechanisms. Proc Natl Acad Sci USA 92:1580–1584
Canals M, Marcellino D, Fanelli F et al (2003) Adenosine A2A-dopamine D2 receptor-receptor heteromerization: qualitative and quantitative assessment by fluorescence and bioluminescence energy transfer. J Biol Chem 278:46741–46749
Cattaneo MG, Scita G, Vicentini LM (1999) Somatostatin inhibits PDGF-stimulated Ras activation in human neuroblastoma cells. FEBS Lett 459:64–68
Cattaneo MG, Taylor JE, Culler MD et al (2000) Selective stimulation of somatostatin receptor subtypes: differential effects on Ras/MAP kinase pathway and cell proliferation in human neuroblastoma cells. FEBS Lett 481:271–276
Cervera P, Videau C, Viollet C et al (2002) Comparison of somatostatin receptor expression in human gliomas and medulloblastomas. J Neuroendocrinol 14:458–471
Cescato R, Schulz S, Waser B et al (2006) Internalization of sst2, sst3, and sst5 receptors: effects of somatostatin agonists and antagonists. J Nucl Med 47:502–511
Cheng ZJ, Miller LJ (2001) Agonist-dependent dissociation of oligomeric complexes of G protein-coupled cholecystokinin receptors demonstrated in living cells using bioluminescence resonance energy transfer. J Biol Chem 276:48040–48047
Chihara K, Arimura A, Schally AV (1979) Effect of intraventricular injection of dopamine, noreprinephrine, acetylcholine, and 5-hydroxytryptamine on immunoreactive somatostatin release into rat hypophyseal portal blood. Endocrinology 104:1656–1662
Ciruela F, Burgueno J, Casado V et al (2004) Combining mass spectrometry and pull-down techniques for the study of receptor heteromerization. Direct epitope-epitope electrostatic interactions between adenosine A2A and dopamine D2 receptors. Anal Chem 76:5354–5363
Claing A, Perry SJ, Achiriloaie M et al (2000) Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity. Proc Natl Acad Sci USA 97:1119–1124
Claing A, Laporte SA, Caron MG et al (2002) Endocytosis of G protein-coupled receptors: roles of G protein-coupled receptor kinases and beta-arrestin proteins. Prog Neurobiol 66:61–79
Cordelier P, Esteve JP, Bousquet C et al (1997) Characterization of the antiproliferative signal mediated by the somatostatin receptor subtype sst5. Proc Natl Acad Sci USA 94:9343–9348
Cox BA, Rosser MP, Kozlowski MR et al (1995) Regulation and functional characterization of a rat recombinant dopamine D3 receptor. Synapse 21:1–9
Cozzi R, Attanasio R, Barausse M et al (1998) Cabergoline in acromegaly: a renewed role for dopamine agonist treatment? Eur J Endocrinol 139:516–521
Csaba Z, Dournaud P (2001) Cellular biology of somatostatin receptors. Neuropeptides 35:1–23
Csaba Z, Bernard V, Helboe L et al (2001) In vivo internalization of the somatostatin sst2A receptor in rat brain: evidence for translocation of cell-surface receptors into the endosomal recycling pathway. Mol Cell Neurosci 17:646–661
Csaba Z, Simon A, Helboe L et al (2002) Neurochemical characterization of receptor-expressing cell populations by in vivo agonist-induced internalization: insights from the somatostatin sst2A receptor. J Comp Neurol 454:192–199
Csaba Z, Simon A, Helboe L et al (2003) Targeting sst2A receptor-expressing cells in the rat hypothalamus through in vivo agonist stimulation: neuroanatomical evidence for a major role of this subtype in mediating somatostatin functions. Endocrinology 144:1564–1573
Cvejic S, Devi LA (1997) Dimerization of the delta opioid receptor: implication for a role in receptor internalization. J Biol Chem 272:26959–26964
Dalm VA, Van Hagen PM, de Krijger RR et al (2004) Distribution pattern of somatostatin and cortistatin mRNA in human central and peripheral tissues. Clin Endocrinol (Oxf) 60:625–629
Danesi R, Del Tacca M (1996) The effects of the somatostatin analog octreotide on angiogenesis in vitro. Metabolism 45:49–50
Danesi R, Agen C, Benelli U et al (1997) Inhibition of experimental angiogenesis by the somatostatin analogue octreotide acetate (SMS 201–995). Clin Cancer Res 3:265–272
Danila DC, Haidar JN, Zhang X et al (2001) Somatostatin receptor-specific analogs: effects on cell proliferation and growth hormone secretion in human somatotroph tumors. J Clin Endocrinol Metab 86:2976–2981
Dasgupta P, Mukherjee R (2000) Lipophilization of somatostatin analog RC-160 with long chain fatty acid improves its antiproliferative and antiangiogenic activity in vitro. Br J Pharmacol 129:101–109
Day R, Dong W, Panetta R et al (1995) Expression of mRNA for somatostatin receptor (sstr) types 2 and 5 in individual rat pituitary cells. A double labeling in situ hybridization analysis. Endocrinology 136:5232–5235
de Herder WW, Lamberts SW (2005) Somatostatin analogs as radiodiagnostic tools. Rev Endocr Metab Disord 6:23–27
de Herder WW, Hofland LJ, van der Lely AJ et al (2003) Somatostatin receptors in gastroentero-pancreatic neuroendocrine tumours. Endocr Relat Cancer 10:451–458
de Lecea L, Criado JR, Prospero-Garcia O et al (1996) A cortical neuropeptide with neuronal depressant and sleep-modulating properties. Nature 381:242–245
de Weille JR, Schmid-Antomarchi H, Fosset M et al (1989) Regulation of ATP-sensitive K+ channels in insulinoma cells: activation by somatostatin and protein kinase C and the role of cAMP. Proc Natl Acad Sci USA 86:2971–2975
Dent P, Wang Y, Gu YZ et al (1997) S49 cells endogenously express subtype 2 somatostatin receptors which couple to increase protein tyrosine phosphatase activity in membranes and down-regulate Raf-1 activity in situ. Cell Signal 9:539–549
Dhanasekaran N, Heasley LE, Johnson GL (1995) G protein-coupled receptor systems involved in cell growth and oncogenesis. Endocr Rev 16:259–270
Djordjijevic D, Zhang J, Priam M et al (1998) Effect of 17beta-estradiol on somatostatin receptor expression and inhibitory effects on growth hormone and prolactin release in rat pituitary cell cultures. Endocrinology 139:2272–2277
Douziech N, Calvo E, Coulombe Z et al (1999) Inhibitory and stimulatory effects of somatostatin on two human pancreatic cancer cell lines: a primary role for tyrosine phosphatase SHP-1. Endocrinology 140:765–777
Dubois MP (1975) Immunoreactive somatostatin is present in discrete cells of the endocrine pancreas. Proc Natl Acad Sci USA 72:1340–1343
Duran-Prado M, Bucharles C, Gonzalez BJ et al (2007) Porcine somatostatin receptor 2 displays typical pharmacological sst2 features but unique dynamics of homodimerization and internalization. Endocrinology 148:411–421
Elliott DE (2004) Expression and function of somatostatin and its receptors in immune cells. In: Srikant CB (ed) Somatostatin. Kluwer, Norwell, pp 169–184
Elliott DE, Metwali A, Blum AM et al (1994) T lymphocytes isolated from the hepatic granulomas of schistosome-infected mice express somatostatin receptor subtype II (SSTR2) messenger RNA. J Immunol 153:1180–1186
Ensinck JW, Laschansky EC, Vogel RE et al (1989) Circulating prosomatostatin-derived peptides. Differential responses to food ingestion. J Clin Invest 83:1580–1589
Epelbaum J, Dournaud P, Fodor M et al (1994) The neurobiology of somatostatin. Crit Rev Neurobiol 8:25–44
Eriksson B, Oberg K (1999) Summing up 15 years of somatostatin analog therapy in neuroendocrine tumors: future outlook. Ann Oncol 10(Suppl 2):S31–S38
Fan T, Varghese G, Nguyen T et al (2005) A role for the distal carboxyl tails in generating the novel pharmacology and G protein activation profile of mu and delta opioid receptor hetero-oligomers. J Biol Chem 280:38478–38488
Fedele M, De Martino I, Pivonello R et al (2007) SOM230, a new somatostatin analogue, is highly effective in the therapy of growth hormone/prolactin-secreting pituitary adenomas. Clin Cancer Res 13:2738–2744
Feniuk W, Jarvie E, Luo J et al (2000) Selective somatostatin sst(2) receptor blockade with the novel cyclic octapeptide, CYN-154806. Neuropharmacology 39:1443–1450
Ferjoux G, Bousquet C, Cordelier P et al (2000) Signal transduction of somatostatin receptors negatively controlling cell proliferation. J Physiol Paris 94:205–210
Ferjoux G, Lopez F, Esteve JP et al (2003) Critical role of Src and SHP-2 in sst2 somatostatin receptor-mediated activation of SHP-1 and inhibition of cell proliferation. Mol Biol Cell 14:3911–3928
Ferland L, Labrie F, Jobin M et al (1976) Physiological role of somatostatin in the control of growth hormone and thyrotropin secretion. Biochem Biophys Res Commun 68:149–156
Ferrante E, Pellegrini C, Bondioni S et al (2006) Octreotide promotes apoptosis in human somatotroph tumor cells by activating somatostatin receptor type 2. Endocr Relat Cancer 13:955–962
Finley JC, Maderdrut JL, Roger LJ et al (1981) The immunocytochemical localization of somatostatin-containing neurons in the rat central nervous system. Neuroscience 6:2173–2192
Florio T (2008) Molecular mechanisms of the antiproliferative activity of somatostatin receptors (SSTRs) in neuroendocrine tumors. Front Biosci 13:822–840
Florio T, Rim C, Hershberger RE et al (1994) The somatostatin receptor SSTR1 is coupled to phosphotyrosine phosphatase activity in CHO-K1 cells. Mol Endocrinol 8:1289–1297
Florio T, Scorziello A, Thellung S et al (1997) Oncogene transformation of PC Cl3 clonal thyroid cell line induces an autonomous pattern of proliferation that correlates with a loss of basal and stimulated phosphotyrosine phosphatase activity. Endocrinology 138:3756–3763
Florio T, Yao H, Carey KD et al (1999) Somatostatin activation of mitogen-activated protein kinase via somatostatin receptor 1 (SSTR1). Mol Endocrinol 13:24–37
Florio T, Thellung S, Arena S et al (2000) Somatostatin receptor 1 (SSTR1)-mediated inhibition of cell proliferation correlates with the activation of the MAP kinase cascade: role of the phosphotyrosine phosphatase SHP-2. J Physiol Paris 94:239–250
Florio T, Arena S, Thellung S et al (2001) The activation of the phosphotyrosine phosphatase eta (r-PTP eta) is responsible for the somatostatin inhibition of PC Cl3 thyroid cell proliferation. Mol Endocrinol 15:1838–1852
Florio T, Morini M, Villa V et al (2003a) Somatostatin inhibits tumor angiogenesis and growth via somatostatin receptor-3-mediated regulation of endothelial nitric oxide synthase and mitogen-activated protein kinase activities. Endocrinology 144:1574–1584
Florio T, Thellung S, Corsaro A et al (2003b) Characterization of the intracellular mechanisms mediating somatostatin and lanreotide inhibition of DNA synthesis and growth hormone release from dispersed human GH-secreting pituitary adenoma cells in vitro. Clin Endocrinol (Oxf) 59:115–128
Franco R, Canals M, Marcellino D et al (2003) Regulation of heptaspanning-membrane-receptor function by dimerization and clustering. Trends Biochem Sci 28:238–243
Frankel BJ, Heldt AM, Grodsky GM (1982) Effects of K+ and arginine on insulin, glucagon, and somatostatin release from the in vitro perfused rat pancreas. Endocrinology 110:428–431
Fukusumi S, Kitada C, Takekawa S et al (1997) Identification and characterization of a novel human cortistatin-like peptide. Biochem Biophys Res Commun 232:157–163
Fuller PJ, Verity K (1989) Somatostatin gene expression in the thymus gland. J Immunol 143:1015–1017
Funckes CL, Minth CD, Deschenes R et al (1983) Cloning and characterization of a mRNA-encoding rat preprosomatostatin. J Biol Chem 258:8781–8787
Garcia de la Torre N, Wass JA, Turner HE (2002) Antiangiogenic effects of somatostatin analogues. Clin Endocrinol (Oxf) 57:425–441
Gardette R, Petit F, Peineau S et al (2004) Molecular evolution of somatostatin genes. In: Srikant CB (ed) Somatostatin. Kluwer, Norwell, pp 123–142
Geci C, How J, Alturaihi H et al (2007) Beta-amyloid increases somatostatin expression in cultured cortical neurons. J Neurochem 101:664–673
German MS, Moss LG, Rutter WJ (1990) Regulation of insulin gene expression by glucose and calcium in transfected primary islet cultures. J Biol Chem 265:22063–22066
Gines S, Hillion J, Torvinen M et al (2000) Dopamine D1 and adenosine A1 receptors form functionally interacting heteromeric complexes. Proc Natl Acad Sci USA 97:8606–8611
Gold SJ, Han MH, Herman AE et al (2003) Regulation of RGS proteins by chronic morphine in rat locus coeruleus. Eur J Neurosci 17:971–980
Goodman RH, Lund PK, Jacobs JW et al (1980) Pre-prosomatostatins. Products of cell-free translations of messenger RNAs from anglerfish islets. J Biol Chem 255:6549–6552
Goodman RH, Lund PK, Barnett FH et al (1981) Intestinal pre-prosomatostatin. Identification of mRNA coding for a precursor by cell-free translations and hybridization with a cloned islet cDNA. J Biol Chem 256:1499–1501
Goodman RH, Jacobs JW, Dee PC et al (1982) Somatostatin-28 encoded in a cloned cDNA obtained from a rat medullary thyroid carcinoma. J Biol Chem 257:1156–1159
Gottero C, Prodam F, Destefanis S et al (2004) Cortistatin-17 and -14 exert the same endocrine activities as somatostatin in humans. Growth Horm IGF Res 14:382–387
Grant M, Collier B, Kumar U (2004a) Agonist-dependent dissociation of human somatostatin receptor 2 dimers: a role in receptor trafficking. J Biol Chem 279:36179–36183
Grant M, Patel RC, Kumar U (2004b) The role of subtype-specific ligand binding and the C-tail domain in dimer formation of human somatostatin receptors. J Biol Chem 279:38636–38643
Grant M, Alturaihi H, Jaquet P et al (2008a) Cell growth inhibition and functioning of human somatostatin receptor type 2 are modulated by receptor heterodimerization. Mol Endocrinol 22:2278–2292
Grant M, Alturaihi H, Jaquet P et al (2008) Cell growth inhibition and functioning of human somatostatin receptor type 2 are modulated by receptor heterodimerization. Mol Endocrinol 22:2278–2292
Greenman Y, Melmed S (1994a) Heterogeneous expression of two somatostatin receptor subtypes in pituitary tumors. J Clin Endocrinol Metab 78:398–403
Greenman Y, Melmed S (1994b) Expression of three somatostatin receptor subtypes in pituitary adenomas: evidence for preferential SSTR5 expression in the mammosomatotroph lineage. J Clin Endocrinol Metab 79:724–729
Gripentrog JM, Kantele KP, Jesaitis AJ et al (2003) Experimental evidence for lack of homodimerization of the G protein-coupled human N-formyl peptide receptor. J Immunol 171:3187–3193
Gromada J, Hoy M, Buschard K et al (2001) Somatostatin inhibits exocytosis in rat pancreatic alpha-cells by G(i2)-dependent activation of calcineurin and depriming of secretory granules. J Physiol 535:519–532
Grozinsky-Glasberg S, Grossman AB, Korbonits M (2008a) The role of somatostatin analogues in the treatment of neuroendocrine tumours. Mol Cell Endocrinol 286:238–250
Grozinsky-Glasberg S, Shimon I, Korbonits M et al (2008b) Somatostatin analogues in the control of neuroendocrine tumours: efficacy and mechanisms. Endocr Relat Cancer 15:701–720
Grozinsky-Glasberg S, Franchi G, Teng M et al (2008c) Octreotide and the mTOR inhibitor RAD001 (everolimus) block proliferation and interact with the Akt-mTOR-p70S6K pathway in a neuro-endocrine tumour cell Line. Neuroendocrinology 87:168–181
Gu YZ, Schonbrunn A (1997) Coupling specificity between somatostatin receptor sst2A and G proteins: isolation of the receptor-G protein complex with a receptor antibody. Mol Endocrinol 11:527–537
Guillermet J, Saint-Laurent N, Rochaix P et al (2003) Somatostatin receptor subtype 2 sensitizes human pancreatic cancer cells to death ligand-induced apoptosis. Proc Natl Acad Sci USA 100:155–160
Gyr K, Beglinger C, Kohler E et al (1987) Circulating somatostatin. Physiological regulator of pancreatic function? J Clin Invest 79:1595–1600
Hansen JL, Sheikh SP (2004) Functional consequences of 7TM receptor dimerization. Eur J Pharm Sci 23:301–317
Hathway GJ, Humphrey PP, Kendrick KM (1999) Evidence that somatostatin sst2 receptors mediate striatal dopamine release. Br J Pharmacol 128:1346–1352
Hayry P, Raisanen A, Ustinov J et al (1993) Somatostatin analog lanreotide inhibits myocyte replication and several growth factors in allograft arteriosclerosis. Faseb J 7:1055–1060
Hellman B, Lernmark A (1969) Inhibition of the in vitro secretion of insulin by an extract of pancreatic alpha-1 cells. Endocrinology 84:1484–1488
Hierowski MT, Liebow C, du Sapin K et al (1985) Stimulation by somatostatin of dephosphorylation of membrane proteins in pancreatic cancer MIA PaCa-2 cell line. FEBS Lett 179:252–256
Hipkin RW, Friedman J, Clark RB et al (1997) Agonist-induced desensitization, internalization, and phosphorylation of the sst2A somatostatin receptor. J Biol Chem 272:13869–13876
Hipkin RW, Wang Y, Schonbrunn A (2000) Protein kinase C activation stimulates the phosphorylation and internalization of the sst2A somatostatin receptor. J Biol Chem 275:5591–5599
Hofland LJ, Lamberts SW (2003) The pathophysiological consequences of somatostatin receptor internalization and resistance. Endocr Rev 24:28–47
Hofland LJ, van Koetsveld PM, Waaijers M et al (1995) Internalization of the radioiodinated somatostatin analog [125I-Tyr3]octreotide by mouse and human pituitary tumor cells: increase by unlabeled octreotide. Endocrinology 136:3698–3706
Hofland LJ, Breeman WA, Krenning EP et al (1999) Internalization of [DOTA degrees, 125I-Tyr3] Octreotide by somatostatin receptor-positive cells in vitro and in vivo: implications for somatostatin receptor-targeted radio-guided surgery. Proc Assoc Am Physicians 111:63–69
Hokfelt T, Efendic S, Hellerstrom C et al (1975) Cellular localization of somatostatin in endocrine-like cells and neurons of the rat with special references to the A1-cells of the pancreatic islets and to the hypothalamus. Acta Endocrinol Suppl (Copenh) 200:5–41
Hook VY, Azaryan AV, Hwang SR et al (1994) Proteases and the emerging role of protease inhibitors in prohormone processing. FASEB J 8:1269–1278
Hortala M, Ferjoux G, Estival A et al (2003) Inhibitory role of the somatostatin receptor SST2 on the intracrine-regulated cell proliferation induced by the 210-amino acid fibroblast growth factor-2 isoform: implication of JAK2. J Biol Chem 278:20574–20581
Horvath S, Palkovits M, Gorcs T et al (1989) Electron microscopic immunocytochemical evidence for the existence of bidirectional synaptic connections between growth hormone-releasing hormone- and somatostatin-containing neurons in the hypothalamus of the rat. Brain Res 481:8–15
Hou C, Gilbert RL, Barber DL (1994) Subtype-specific signaling mechanisms of somatostatin receptors SSTR1 and SSTR2. J Biol Chem 269:10357–10362
Hoyer D, Nunn C, Hannon J et al (2004) SRA880, in vitro characterization of the first non-peptide somatostatin sst(1) receptor antagonist. Neurosci Lett 361:132–135
Hukovic N, Panetta R, Kumar U et al (1996) Agonist-dependent regulation of cloned human somatostatin receptor types 1–5 (hSSTR1–5): subtype selective internalization or upregulation. Endocrinology 137:4046–4049
Hukovic N, Panetta R, Kumar U et al (1998) The cytoplasmic tail of the human somatostatin receptor type 5 is crucial for interaction with adenylyl cyclase and in mediating desensitization and internalization. J Biol Chem 273:21416–21422
Hukovic N, Rocheville M, Kumar U et al (1999) Agonist-dependent up-regulation of human somatostatin receptor type 1 requires molecular signals in the cytoplasmic C-tail. J Biol Chem 274:24550–24558
Ikeda SR, Schofield GG (1989) Somatostatin blocks a calcium current in rat sympathetic ganglion neurones. J Physiol 409:221–240
Jais P, Terris B, Ruszniewski P et al (1997) Somatostatin receptor subtype gene expression in human endocrine gastroentero-pancreatic tumours. Eur J Clin Invest 27:639–644
James RA, Sarapura VD, Bruns C et al (1997) Thyroid hormone-induced expression of specific somatostatin receptor subtypes correlates with involution of the TtT-97 murine thyrotrope tumor. Endocrinology 138:719–724
James JR, Oliveira MI, Carmo AM et al (2006) A rigorous experimental framework for detecting protein oligomerization using bioluminescence resonance energy transfer. Nat Methods 3:1001–1006
Jaquet P, Ouafik L, Saveanu A et al (1999) Quantitative and functional expression of somatostatin receptor subtypes in human prolactinomas. J Clin Endocrinol Metab 84:3268–3276
Jaquet P, Saveanu A, Gunz G et al (2000) Human somatostatin receptor subtypes in acromegaly: distinct patterns of messenger ribonucleic acid expression and hormone suppression identify different tumoral phenotypes. J Clin Endocrinol Metab 85:781–792
Jaquet P, Gunz G, Saveanu A et al (2005) Efficacy of chimeric molecules directed towards multiple somatostatin and dopamine receptors on inhibition of GH and prolactin secretion from GH-secreting pituitary adenomas classified as partially responsive to somatostatin analog therapy. Eur J Endocrinol 153:135–141
Jiang H, Betancourt L, Smith RG (2006) Ghrelin amplifies dopamine signaling by cross talk involving formation of growth hormone secretagogue receptor/dopamine receptor subtype 1 heterodimers. Mol Endocrinol 20:1772–1785
Johansson O, Hokfelt T, Elde RP (1984) Immunohistochemical distribution of somatostatin-like immunoreactivity in the central nervous system of the adult rat. Neuroscience 13:265–339
Joseph-Bravo P, Charli JL, Sherman T et al (1980) Identification of a putative hypothalamic mRNA coding for somatostatin and of its product in cell-free translation. Biochem Biophys Res Commun 94:1004–1012
Kanatsuka A, Makino H, Matsushima Y et al (1981) Effect of calcium on the secretion of somatostatin and insulin from pancreatic islets. Endocrinology 108:2254–2257
Karalis K, Mastorakos G, Chrousos GP et al (1994) Somatostatin analogues suppress the inflammatory reaction in vivo. J Clin Invest 93:2000–2006
Katakami H, Downs TR, Frohman LA (1988) Inhibitory effect of hypothalamic medial preoptic area somatostatin on growth hormone-releasing factor in the rat. Endocrinology 123:1103–1109
Kearn CS, Blake-Palmer K, Daniel E et al (2005) Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors enhances heterodimer formation: a mechanism for receptor cross-talk? Mol Pharmacol 67:1697–1704
Kendall DM, Poitout V, Olson LK et al (1995) Somatostatin coordinately regulates glucagon gene expression and exocytosis in HIT-T15 cells. J Clin Invest 96:2496–2502
Kimura N, Tomizawa S, Arai KN et al (1998) Chronic treatment with estrogen up-regulates expression of sst2 messenger ribonucleic acid (mRNA) but down-regulates expression of sst5 mRNA in rat pituitaries. Endocrinology 139:1573–1580
Kleinman R, Gingerich R, Ohning G et al (1995) The influence of somatostatin on glucagon and pancreatic polypeptide secretion in the isolated perfused human pancreas. Int J Pancreatol 18:51–57
Kleuss C, Hescheler J, Ewel C et al (1991) Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents. Nature 353:43–48
Koenig JA, Edwardson JM, Humphrey PP (1997) Somatostatin receptors in Neuro2A neuroblastoma cells: ligand internalization. Br J Pharmacol 120:52–59
Koerker DJ, Ruch W, Chideckel E et al (1974) Somatostatin: hypothalamic inhibitor of the endocrine pancreas. Science 184:482–484
Koizumi M, Onda M, Tanaka N et al (2002) Antiangiogenic effect of octreotide inhibits the growth of human rectal neuroendocrine carcinoma. Digestion 65:200–206
Kreienkamp HJ, Roth A, Richter D (1998) Rat somatostatin receptor subtype 4 can be made sensitive to agonist-induced internalization by mutation of a single threonine (residue 331). DNA Cell Biol 17:869–878
Kreienkamp HJ, Liew CW, Bachner D et al (2004) Physiology of somatostatin receptors: from genetics to molecular analysis. In: Srikant CB (ed) Somatostatin. Kluwer, Norwell, pp 185–202
Kreuzer OJ, Krisch B, Dery O et al (2001) Agonist-mediated endocytosis of rat somatostatin receptor subtype 3 involves beta-arrestin and clathrin coated vesicles. J Neuroendocrinol 13:279–287
Krisch B, Feindt J, Mentlein R (1998) Immunoelectronmicroscopic analysis of the ligand-induced internalization of the somatostatin receptor subtype 2 in cultured human glioma cells. J Histochem Cytochem 46:1233–1242
Kroeger KM, Pfleger KD, Eidne KA (2003) G-protein coupled receptor oligomerization in neuroendocrine pathways. Front Neuroendocrinol 24:254–278
Krulich L, Dhariwal AP, McCann SM (1968) Stimulatory and inhibitory effects of purified hypothalamic extracts on growth hormone release from rat pituitary in vitro. Endocrinology 83:783–790
Kumar U (2004) Characterization of striatal cultures with the effect of QUIN and NMDA. Neurosci Res 49:29–38
Kumar U (2005) Expression of somatostatin receptor subtypes (SSTR1–5) in Alzheimer’s disease brain: an immunohistochemical analysis. Neuroscience 134:525–538
Kumar U (2007) Colocalization of somatostatin receptor subtypes (SSTR1–5) with somatostatin, NADPH-diaphorase (NADPH-d), and tyrosine hydroxylase in the rat hypothalamus. J Comp Neurol 504:185–205
Kumar U (2008) Somatostatin in medium-sized aspiny interneurons of striatum is responsible for their preservation in quinolinic acid and N-methyl-d-asparate-induced neurotoxicity. J Mol Neurosci 35:345–354
Kumar U, Asotra K, Patel SC et al (1997) Expression of NMDA receptor-1 (NR1) and huntingtin in striatal neurons which colocalize somatostatin, neuropeptide Y, and NADPH diaphorase: a double-label histochemical and immunohistochemical study. Exp Neurol 145:412–424
Kumar U, Sasi R, Suresh S et al (1999) Subtype-selective expression of the five somatostatin receptors (hSSTR1–5) in human pancreatic islet cells: a quantitative double-label immunohistochemical analysis. Diabetes 48:77–85
Kuner R, Kohr G, Grunewald S et al (1999) Role of heteromer formation in GABAB receptor function. Science 283:74–77
Kwekkeboom DJ, de Jong M, Krenning EP (2004) Somatostatin receptor imaging. In: Srikant CB (ed) Somatostatin. Kluwer, Norwell, pp 203–214
Labeur M, Theodoropoulou M, Sievers C et al (2006) New aspects in the diagnosis and treatment of Cushing disease. Front Horm Res 35:169–178
Lahlou H, Saint-Laurent N, Esteve JP et al (2003) sst2 Somatostatin receptor inhibits cell proliferation through Ras-, Rap1-, and B-Raf-dependent ERK2 activation. J Biol Chem 278:39356–39371
Lamberts SW, Krenning EP, Reubi JC (1991) The role of somatostatin and its analogs in the diagnosis and treatment of tumors. Endocr Rev 12:450–482
Lamberts SW, van der Lely AJ, de Herder WW et al (1996) Octreotide. N Engl J Med 334:246–254
Lamberts SW, de Herder WW, Hofland LJ (2002) Somatostatin analogs in the diagnosis and treatment of cancer. Trends Endocrinol Metab 13:451–457
Latif R, Graves P, Davies TF (2002) Ligand-dependent inhibition of oligomerization at the human thyrotropin receptor. J Biol Chem 277:45059–45067
Law PY, Erickson-Herbrandson LJ, Zha QQ et al (2005) Heterodimerization of mu- and delta-opioid receptors occurs at the cell surface only and requires receptor-G protein interactions. J Biol Chem 280:11152–11164
Lefkowitz RJ (2004) Historical review: a brief history and personal retrospective of seven-transmembrane receptors. Trends Pharmacol Sci 25:413–422
Lefkowitz RJ, Shenoy SK (2005) Transduction of receptor signals by beta-arrestins. Science 308:512–517
Liapakis G, Hoeger C, Rivier J et al (1996) Development of a selective agonist at the somatostatin receptor subtype sstr1. J Pharmacol Exp Ther 276:1089–1094
Lin CY, Varma MG, Joubel A et al (2003) Conserved motifs in somatostatin, D2-dopamine, and alpha 2B-adrenergic receptors for inhibiting the Na-H exchanger, NHE1. J Biol Chem 278:15128–15135
Liu Q, Schonbrunn A (2001) Agonist-induced phosphorylation of somatostatin receptor subtype 1 (sst1). Relationship to desensitization and internalization. J Biol Chem 276:3709–3717
Liu YF, Jakobs KH, Rasenick MM et al (1994) G protein specificity in receptor-effector coupling. Analysis of the roles of G0 and Gi2 in GH4C1 pituitary cells. J Biol Chem 269:13880–13886
Liu D, Martino G, Thangaraju M et al (2000) Caspase-8-mediated intracellular acidification precedes mitochondrial dysfunction in somatostatin-induced apoptosis. J Biol Chem 275:9244–9250
Lohse MJ, Benovic JL, Codina J et al (1990) Beta-arrestin: a protein that regulates beta-adrenergic receptor function. Science 248:1547–1550
Lopez F, Esteve JP, Buscail L et al (1997) The tyrosine phosphatase SHP-1 associates with the sst2 somatostatin receptor and is an essential component of sst2-mediated inhibitory growth signaling. J Biol Chem 272:24448–24454
Lopez F, Ferjoux G, Cordelier P et al (2001) Neuronal nitric oxide synthase: a substrate for SHP-1 involved in sst2 somatostatin receptor growth inhibitory signaling. FASEB J 15:2300–2302
Losa M, Ciccarelli E, Mortini P et al (2001) Effects of octreotide treatment on the proliferation and apoptotic index of GH-secreting pituitary adenomas. J Clin Endocrinol Metab 86:5194–5200
Low MJ, Otero-Corchon V, Parlow AF et al (2001) Somatostatin is required for masculinization of growth hormone-regulated hepatic gene expression but not of somatic growth. J Clin Invest 107:1571–1580
Luft R, Efendic S, Hokfelt T et al (1974) Immunohistochemical evidence for the localization of somatostatin-like immunoreactivity in a cell population of the pancreatic islets. Med Biol 52:428–430
Mandarino L, Stenner D, Blanchard W et al (1981) Selective effects of somatostatin-14, -25 and -28 on in vitro insulin and glucagon secretion. Nature 291:76–77
Marks N, Stern F, Benuck M (1976) Correlation between biological potency and biodegradation of a somatostatin analogue. Nature 261:511–512
Marzullo P, Ferone D, Di Somma C et al (1999) Efficacy of combined treatment with lanreotide and cabergoline in selected therapy-resistant acromegalic patients. Pituitary 1:115–120
Massa A, Barbieri F, Aiello C et al (2004a) The expression of the phosphotyrosine phosphatase DEP-1/PTPeta dictates the responsivity of glioma cells to somatostatin inhibition of cell proliferation. J Biol Chem 279:29004–29012
Massa A, Barbieri F, Aiello C et al (2004b) The phosphotyrosine phosphatase eta mediates somatostatin inhibition of glioma proliferation via the dephosphorylation of ERK1/2. Ann N Y Acad Sci 1030:264–274
Maurer R, Gaehwiler BH, Buescher HH et al (1982) Opiate antagonistic properties of an octapeptide somatostatin analog. Proc Natl Acad Sci USA 79:4815–4817
McGraw DW, Mihlbachler KA, Schwarb MR et al (2006) Airway smooth muscle prostaglandin-EP1 receptors directly modulate beta2-adrenergic receptors within a unique heterodimeric complex. J Clin Invest 116:1400–1409
Mellado M, Rodriguez-Frade JM, Vila-Coro AJ et al (2001) Chemokine receptor homo- or heterodimerization activates distinct signaling pathways. Embo J 20:2497–2507
Melmed S, Sternberg R, Cook D et al (2005) A critical analysis of pituitary tumor shrinkage during primary medical therapy in acromegaly. J Clin Endocrinol Metab 90:4405–4410
Meriney SD, Gray DB, Pilar GR (1994) Somatostatin-induced inhibition of neuronal Ca2+ current modulated by cGMP-dependent protein kinase. Nature 369:336–339
Meyer BH, Segura JM, Martinez KL et al (2006) FRET imaging reveals that functional neurokinin-1 receptors are monomeric and reside in membrane microdomains of live cells. Proc Natl Acad Sci USA 103:2138–2143
Meyerhof W (1998) The elucidation of somatostatin receptor functions: a current view. Rev Physiol Biochem Pharmacol 133:55–108
Miller GM, Alexander JM, Bikkal HA et al (1995) Somatostatin receptor subtype gene expression in pituitary adenomas. J Clin Endocrinol Metab 80:1386–1392
Milligan G (2008) A day in the life of a G protein-coupled receptor: the contribution to function of G protein-coupled receptor dimerization. Br J Pharmacol 153(Suppl 1):S216–S229
Moller LN, Stidsen CE, Hartmann B et al (2003) Somatostatin receptors. Biochim Biophys Acta 1616:1–84
Montminy MR, Low MJ, Tapia-Arancibia L et al (1986) Cyclic AMP regulates somatostatin mRNA accumulation in primary diencephalic cultures and in transfected fibroblast cells. J Neurosci 6:1171–1176
Morel G, Leroux P, Pelletier G (1985) Ultrastructural autoradiographic localization of somatostatin-28 in the rat pituitary gland. Endocrinology 116:1615–1620
Mouchantaf R, Kumar U, Sulea T et al (2001) A conserved alpha-helix at the amino terminus of prosomatostatin serves as a sorting signal for the regulated secretory pathway. J Biol Chem 276:26308–26316
Mouchantaf R, Patel YC, Kumar U (2004a) Processing and intracellular targeting of somatostatin. In: Srikant CB (ed) Somatostatin. Kluwer, Norwell, pp 16–27
Mouchantaf R, Watt HL, Sulea T et al (2004b) Prosomatostatin is proteolytically processed at the amino terminal segment by subtilase SKI-1. Regul Pept 120:133–140
Murray RD, Kim K, Ren SG et al (2004) Central and peripheral actions of somatostatin on the growth hormone-IGF-I axis. J Clin Invest 114:349–356
Neel NF, Schutyser E, Sai J et al (2005) Chemokine receptor internalization and intracellular trafficking. Cytokine Growth Factor Rev 16:637–658
Nelson-Piercy C, Hammond PJ, Gwilliam ME et al (1994) Effect of a new oral somatostatin analog (SDZ CO 611) on gastric emptying, mouth to cecum transit time, and pancreatic and gut hormone release in normal male subjects. J Clin Endocrinol Metab 78:329–336
Ng GY, Varghese G, Chung HT et al (1997) Resistance of the dopamine D2L receptor to desensitization accompanies the up-regulation of receptors on to the surface of Sf9 cells. Endocrinology 138:4199–4206
Nichols B (2003) Caveosomes and endocytosis of lipid rafts. J Cell Sci 116:4707–4714
Nouel D, Gaudriault G, Houle M et al (1997) Differential internalization of somatostatin in COS-7 cells transfected with SST1 and SST2 receptor subtypes: a confocal microscopic study using novel fluorescent somatostatin derivatives. Endocrinology 138:296–306
Nunn C, Langenegger D, Hurth K et al (2003) Agonist properties of putative small-molecule somatostatin sst2 receptor-selective antagonists. Eur J Pharmacol 465:211–218
O’Carroll AM, Krempels K (1995) Widespread distribution of somatostatin receptor messenger ribonucleic acids in rat pituitary. Endocrinology 136:5224–5227
Olias G, Viollet C, Kusserow H et al (2004) Regulation and function of somatostatin receptors. J Neurochem 89:1057–1091
Oomen SP, Hofland LJ, Lamberts SW et al (2001) Internalization-defective mutants of somatostatin receptor subtype 2 exert normal signaling functions in hematopoietic cells. FEBS Lett 503:163–167
Orci L, Baetens D, Dubois MP et al (1975) Evidence for the D-cell of the pancreas secreting somatostatin. Horm Metab Res 7:400–402
Oyama H, O’Connell K, Permutt A (1980) Cell-mediated synthesis of somatostatin. Endocrinology 107:845–847
Pagliacci MC, Tognellini R, Grignani F et al (1991) Inhibition of human breast cancer cell (MCF-7) growth in vitro by the somatostatin analog SMS 201–995: effects on cell cycle parameters and apoptotic cell death. Endocrinology 129:2555–2562
Panetta R, Patel YC (1995) Expression of mRNA for all five human somatostatin receptors (hSSTR1–5) in pituitary tumors. Life Sci 56:333–342
Papotti M, Tarabra E, Allia E et al (2003) Presence of cortistatin in the human pancreas. J Endocrinol Invest 26:RC15–RC18
Park C, Yang I, Woo J et al (2004) Somatostatin (SRIF) receptor subtype 2 and 5 gene expression in growth hormone-secreting pituitary adenomas: the relationship with endogenous srif activity and response to octreotide. Endocr J 51:227–236
Patch D, Burroughs A (2002) Vapreotide in variceal bleeding. J Hepatol 37:167–168
Patel YC (1992) General aspects of the biology and function of somatostatin. In: Weil C, Muller EE, Thorner MO (eds) Basic and clinical aspects of neuroscience. Springer, Berlin, pp 1–16
Patel YC (1997) Molecular pharmacology of somatostatin receptor subtypes. J Endocrinol Invest 20:348–367
Patel YC (1999) Somatostatin and its receptor family. Front Neuroendocrinol 20:157–198
Patel YC, O’Neil W (1988) Peptides derived from cleavage of prosomatostatin at carboxyl- and amino-terminal segments. Characterization of tissue and secreted forms in the rat. J Biol Chem 263:745–751
Patel YC, Reichlin S (1978) Somatostatin in hypothalamus, extrahypothalamic brain, and peripheral tissues of the rat. Endocrinology 102:523–530
Patel YC, Wheatley T, Ning C (1981) Multiple forms of immunoreactive somatostatin: comparison of distribution in neural and nonneural tissues and portal plasma of the rat. Endocrinology 109:1943–1949
Patel YC, Murthy KK, CB EEE et al (1990) Mechanism of action of somatostatin: an overview of receptor function and studies of the molecular characterization and purification of somatostatin receptor proteins. Metabolism 39:63–69
Patel YC, Papachristou DN, Zingg HH et al (1991) Regulation of islet somatostatin secretion and gene expression: selective effects of adenosine 3′, 5′-monophosphate and phorbol esters in normal islets of Langerhans and in a somatostatin-producing rat islet clonal cell line 1027 B2. Endocrinology 128:1754–1762
Patel YC, Greenwood M, Kent G et al (1993) Multiple gene transcripts of the somatostatin receptor SSTR2: tissue selective distribution and cAMP regulation. Biochem Biophys Res Commun 192:288–294
Patel YC, Greenwood MT, Warszynska A et al (1994) All five cloned human somatostatin receptors (hSSTR1–5) are functionally coupled to adenylyl cyclase. Biochem Biophys Res Commun 198:605–612
Patel YC, Greenwood MT, Panetta R et al (1995) The somatostatin receptor family. Life Sci 57:1249–1265
Patel YC, Greenwood M, Panetta R et al (1996) Molecular biology of somatostatin receptor subtypes. Metabolism 45:31–38
Patel YC, Liu JL, Galanopoulou AS et al (2001) Production, action, and degradation of somatostatin. In: Jefferson LS, Cherrington AD (eds) Handbook of physiology, the endocrine pancreas and regulation of metabolism. Oxford University Press, New York
Patel RC, Kumar U, Lamb DC et al (2002) Ligand binding to somatostatin receptors induces receptor-specific oligomer formation in live cells. Proc Natl Acad Sci USA 99:3294–3299
Patzelt C, Tager HS, Carroll RJ et al (1980) Identification of prosomatostatin in pancreatic islets. Proc Natl Acad Sci USA 77:2410–2414
Peeters TL, Depraetere Y, Vantrappen GR (1981) Simple extraction method and radioimmunoassay for somatostatin in human plasma. Clin Chem 27:888–891
Pelletier G, Leclerc R, Arimura A et al (1975) Letter: immunohistochemical localization of somatostatin in the rat pancreas. J Histochem Cytochem 23:699–702
Pello OM, Martinez-Munoz L, Parrillas V et al (2008) Ligand stabilization of CXCR4/delta-opioid receptor heterodimers reveals a mechanism for immune response regulation. Eur J Immunol 38:537–549
Penman E, Wass JA, Medbak S et al (1981) Response of circulating immunoreactive somatostatin to nutritional stimuli in normal subjects. Gastroenterology 81:692–699
Perron A, Chen ZG, Gingras D et al (2003) Agonist-independent desensitization and internalization of the human platelet-activating factor receptor by coumermycin-gyrase B-induced dimerization. J Biol Chem 278:27956–27965
Pfeiffer M, Koch T, Schroder H et al (2001) Homo- and heterodimerization of somatostatin receptor subtypes. Inactivation of sst(3) receptor function by heterodimerization with sst(2A). J Biol Chem 276:14027–14036
Pfeiffer M, Koch T, Schroder H et al (2002) Heterodimerization of somatostatin and opioid receptors cross-modulates phosphorylation, internalization, and desensitization. J Biol Chem 277:19762–19772
Philippe J (1993) Somatostatin inhibits insulin-gene expression through a posttranscriptional mechanism in a hamster islet cell line. Diabetes 42:244–249
Pierce KL, Premont RT, Lefkowitz RJ (2002) Seven-transmembrane receptors. Nat Rev Mol Cell Biol 3:639–650
Poitout L, Roubert P, Contour-Galcera MO et al (2001) Identification of potent non-peptide somatostatin antagonists with sst(3) selectivity. J Med Chem 44:2990–3000
Polak JM, Pearse AG, Grimelius L et al (1975) Growth-hormone release-inhibiting hormone in gastrointestinal and pancreatic D cells. Lancet 1:1220–1222
Pradayrol L, Jornvall H, Mutt V et al (1980) N-terminally extended somatostatin: the primary structure of somatostatin-28. FEBS Lett 109:55–58
Premont RT, Gainetdinov RR (2007) Physiological roles of G protein-coupled receptor kinases and arrestins. Annu Rev Physiol 69:511–534
Presky DH, Schonbrunn A (1988) Somatostatin pretreatment increases the number of somatostatin receptors in GH4C1 pituitary cells and does not reduce cellular responsiveness to somatostatin. J Biol Chem 263:714–721
Prinster SC, Hague C, Hall RA (2005) Heterodimerization of g protein-coupled receptors: specificity and functional significance. Pharmacol Rev 57:289–298
Putney LK, Denker SP, Barber DL (2002) The changing face of the Na+/H+ exchanger, NHE1: structure, regulation, and cellular actions. Annu Rev Pharmacol Toxicol 42:527–552
Qanbar R, Bouvier M (2003) Role of palmitoylation/depalmitoylation reactions in G-protein-coupled receptor function. Pharmacol Ther 97:1–33
Quintela M, Senaris RM, Dieguez C (1997) Transforming growth factor-betas inhibit somatostatin messenger ribonucleic acid levels and somatostatin secretion in hypothalamic cells in culture. Endocrinology 138:4401–4409
Rabbani SN, Patel YC (1990) Peptides derived by processing of rat prosomatostatin near the amino-terminus: characterization, tissue distribution, and release. Endocrinology 126:2054–2061
Rasmussen SG, Choi HJ, Rosenbaum DM et al (2007) Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. Nature 450:383–387
Ravazzola M, Benoit R, Ling N et al (1989) Prosomatostatin-derived antrin is present in gastric D cells and in portal blood. J Clin Invest 83:362–366
Reardon DB, Dent P, Wood SL et al (1997) Activation in vitro of somatostatin receptor subtypes 2, 3, or 4 stimulates protein tyrosine phosphatase activity in membranes from transfected Ras-transformed NIH 3T3 cells: coexpression with catalytically inactive SHP-2 blocks responsiveness. Mol Endocrinol 11:1062–1069
Redmon JB, Towle HC, Robertson RP (1994) Regulation of human insulin gene transcription by glucose, epinephrine, and somatostatin. Diabetes 43:546–551
Reichlin S (1983a) Somatostatin (second of two parts). N Engl J Med 309:1556–1563
Reichlin S (1983b) Somatostatin. N Engl J Med 309:1495–1501
Reisine T, Axelrod J (1983) Prolonged somatostatin pretreatment desensitizes somatostatin’s inhibition of receptor-mediated release of adrenocorticotropin hormone and sensitizes adenylate cyclase. Endocrinology 113:811–813
Reisine T, Bell GI (1995) Molecular biology of somatostatin receptors. Endocr Rev 16:427–442
Ren SG, Taylor J, Dong J et al (2003) Functional association of somatostatin receptor subtypes 2 and 5 in inhibiting human growth hormone secretion. J Clin Endocrinol Metab 88:4239–4245
Resmini E, Dadati P, Ravetti JL et al (2007) Rapid pituitary tumor shrinkage with dissociation between antiproliferative and antisecretory effects of a long-acting octreotide in an acromegalic patient. J Clin Endocrinol Metab 92:1592–1599
Reubi JC, Landolt AM (1984) High density of somatostatin receptors in pituitary tumors from acromegalic patients. J Clin Endocrinol Metab 59:1148–1151
Reubi JC, Hacki WH, Lamberts SW (1987) Hormone-producing gastrointestinal tumors contain a high density of somatostatin receptors. J Clin Endocrinol Metab 65:1127–1134
Reubi JC, Schaer JC, Wenger S et al (2000) SST3-selective potent peptidic somatostatin receptor antagonists. Proc Natl Acad Sci USA 97:13973–13978
Reubi JC, Waser B, Schaer JC (2004) Expression of somatostatin receptors in human tissue in health and disease. In: Srikant CB (ed) Somatostatin. Kluwer, Norwell, pp 107–121
Rocheville M, Lange DC, Kumar U et al (2000a) Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity. Science 288:154–157
Rocheville M, Lange DC, Kumar U et al (2000b) Subtypes of the somatostatin receptor assemble as functional homo- and heterodimers. J Biol Chem 275:7862–7869
Rodriguez-Arnao MD, Gomez-Pan A, Rainbow SJ et al (1981) Effects of prosomatostatin on growth hormone and prolactin response to arginine in man. Comparison with somatostatin. Lancet 1:353–356
Rodriguez-Frade JM, del Real G, Serrano A et al (2004) Blocking HIV-1 infection via CCR5 and CXCR4 receptors by acting in trans on the CCR2 chemokine receptor. EMBO J 23:66–76
Rodriguez-Sanchez MN, Puebla L, Lopez-Sanudo S et al (1997) Dopamine enhances somatostatin receptor-mediated inhibition of adenylate cyclase in rat striatum and hippocampus. J Neurosci Res 48:238–248
Rohrer SP, Birzin ET, Mosley RT et al (1998) Rapid identification of subtype-selective agonists of the somatostatin receptor through combinatorial chemistry. Science 282:737–740
Roosterman D, Roth A, Kreienkamp HJ et al (1997) Distinct agonist-mediated endocytosis of cloned rat somatostatin receptor subtypes expressed in insulinoma cells. J Neuroendocrinol 9:741–751
Roth A, Kreienkamp HJ, Meyerhof W et al (1997a) Phosphorylation of four amino acid residues in the carboxyl terminus of the rat somatostatin receptor subtype 3 is crucial for its desensitization and internalization. J Biol Chem 272:23769–23774
Roth A, Kreienkamp HJ, Nehring RB et al (1997b) Endocytosis of the rat somatostatin receptors: subtype discrimination, ligand specificity, and delineation of carboxy-terminal positive and negative sequence motifs. DNA Cell Biol 16:111–119
Saito T, Iwata N, Tsubuki S et al (2005) Somatostatin regulates brain amyloid beta peptide Abeta42 through modulation of proteolytic degradation. Nat Med 11:434–439
Samuels MH, Henry P, Ridgway EC (1992) Effects of dopamine and somatostatin on pulsatile pituitary glycoprotein secretion. J Clin Endocrinol Metab 74:217–222
Saveanu A, Gunz G, Dufour H et al (2001) Bim-23244, a somatostatin receptor subtype 2- and 5-selective analog with enhanced efficacy in suppressing growth hormone (GH) from octreotide-resistant human GH-secreting adenomas. J Clin Endocrinol Metab 86:140–145
Saveanu A, Lavaque E, Gunz G et al (2002) Demonstration of enhanced potency of a chimeric somatostatin-dopamine molecule, BIM-23A387, in suppressing growth hormone and prolactin secretion from human pituitary somatotroph adenoma cells. J Clin Endocrinol Metab 87:5545–5552
Saveanu A, Gunz G, Guillen S et al (2006) Somatostatin and dopamine-somatostatin multiple ligands directed towards somatostatin and dopamine receptors in pituitary adenomas. Neuroendocrinology 83:258–263
Saveanu A, Jaquet P, Brue T et al (2008) Relevance of coexpression of somatostatin and dopamine D2 receptors in pituitary adenomas. Mol Cell Endocrinol 286:206–213
Scarborough DE, Lee SL, Dinarello CA et al (1989) Interleukin-1 beta stimulates somatostatin biosynthesis in primary cultures of fetal rat brain. Endocrinology 124:549–551
Schaer JC, Waser B, Mengod G et al (1997) Somatostatin receptor subtypes sst1, sst2, sst3 and sst5 expression in human pituitary, gastroentero-pancreatic and mammary tumors: comparison of mRNA analysis with receptor autoradiography. Int J Cancer 70:530–537
Schonbrunn A, Tashjian H Jr (1978) Characterization of functional receptors for somatostatin in rat pituitary cells in culture. J Biol Chem 253:6473–6483
Schreff M, Schulz S, Handel M et al (2000) Distribution, targeting, and internalization of the sst4 somatostatin receptor in rat brain. J Neurosci 20:3785–3797
Schusdziarra V, Dobbs RE, Harris V et al (1977) Immunoreactive somatostatin levels in plasma of normal and alloxan diabetic dogs. FEBS Lett 81:69–72
Seidah NG, Chretien M (1999) Proprotein and prohormone convertases: a family of subtilases generating diverse bioactive polypeptides. Brain Res 848:45–62
Sellers LA, Alderton F, Carruthers AM et al (2000) Receptor isoforms mediate opposing proliferative effects through gbetagamma-activated p38 or Akt pathways. Mol Cell Biol 20:5974–5985
Senaris RM, Lago F, Dieguez C (1996) Gonadal regulation of somatostatin receptor 1, 2 and 3 mRNA levels in the rat anterior pituitary. Brain Res Mol Brain Res 38:171–175
Sharif N, Gendron L, Wowchuk J et al (2007) Coexpression of somatostatin receptor subtype 5 affects internalization and trafficking of somatostatin receptor subtype 2. Endocrinology 148:2095–2105
Sharma K, Srikant CB (1998a) Induction of wild-type p53, Bax, and acidic endonuclease during somatostatin-signaled apoptosis in MCF-7 human breast cancer cells. Int J Cancer 76:259–266
Sharma K, Srikant CB (1998b) G protein coupled receptor signaled apoptosis is associated with activation of a cation insensitive acidic endonuclease and intracellular acidification. Biochem Biophys Res Commun 242:134–140
Sharma K, Patel YC, Srikant CB (1996) Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3. Mol Endocrinol 10:1688–1696
Sharma K, Patel YC, Srikant CB (1999) C-terminal region of human somatostatin receptor 5 is required for induction of Rb and G1 cell cycle arrest. Mol Endocrinol 13:82–90
Shen LP, Pictet RL, Rutter WJ (1982) Human somatostatin I: sequence of the cDNA. Proc Natl Acad Sci USA 79:4575–4579
Shields D (1980) In vitro biosynthesis of somatostatin. Evidence for two distinct preprosomatostatin molecules. J Biol Chem 255:11625–11628
Shimon I, Yan X, Taylor JE et al (1997a) Somatostatin receptor (SSTR) subtype-selective analogues differentially suppress in vitro growth hormone and prolactin in human pituitary adenomas. Novel potential therapy for functional pituitary tumors. J Clin Invest 100:2386–2392
Shimon I, Taylor JE, Dong JZ et al (1997b) Somatostatin receptor subtype specificity in human fetal pituitary cultures. Differential role of SSTR2 and SSTR5 for growth hormone, thyroid-stimulating hormone, and prolactin regulation. J Clin Invest 99:789–798
Shoelson SE, Polonsky KS, Nakabayashi T et al (1986) Circulating forms of somatostatinlike immunoreactivity in human plasma. Am J Physiol 250:E428–E434
Shojamanesh H, Gibril F, Louie A et al (2002) Prospective study of the antitumor efficacy of long-term octreotide treatment in patients with progressive metastatic gastrinoma. Cancer 94:331–343
Siler TM, Yen SC, Vale W et al (1974) Inhibition by somatostatin on the release of TSH induced in man by thyrotropin-releasing factor. J Clin Endocrinol Metab 38:742–745
Sims SM, Lussier BT, Kraicer J (1991) Somatostatin activates an inwardly rectifying K+ conductance in freshly dispersed rat somatotrophs. J Physiol 441:615–637
Skamene A, Patel YC (1984) Infusion of graded concentrations of somatostatin in man: pharmacokinetics and differential inhibitory effects on pituitary and islet hormones. Clin Endocrinol (Oxf) 20:555–564
Smalley KS, Feniuk W, Humphrey PP (1998) Differential agonist activity of somatostatin and L-362855 at human recombinant sst4 receptors. Br J Pharmacol 125:833–841
Smalley KS, Feniuk W, Sellers LA et al (1999) The pivotal role of phosphoinositide-3 kinase in the human somatostatin sst(4) receptor-mediated stimulation of p44/p42 mitogen-activated protein kinase and extracellular acidification. Biochem Biophys Res Commun 263:239–243
Smalley KS, Koenig JA, Feniuk W et al (2001) Ligand internalization and recycling by human recombinant somatostatin type 4 (h sst(4)) receptors expressed in CHO-K1 cells. Br J Pharmacol 132:1102–1110
Song GJ, Hinkle PM (2005) Regulated dimerization of the thyrotropin-releasing hormone receptor affects receptor trafficking but not signaling. Mol Endocrinol 19:2859–2870
Spier AD, de Lecea L (2000) Cortistatin: a member of the somatostatin neuropeptide family with distinct physiological functions. Brain Res Brain Res Rev 33:228–241
Srikant CB (1995) Cell cycle dependent induction of apoptosis by somatostatin analog SMS 201–995 in AtT-20 mouse pituitary cells. Biochem Biophys Res Commun 209:400–406
Srikant CB, Patel YC (1981) Receptor binding of somatostatin-28 is tissue specific. Nature 294:259–260
Srikant CB, Shen SH (1996) Octapeptide somatostatin analog SMS 201–995 induces translocation of intracellular PTP1C to membranes in MCF-7 human breast adenocarcinoma cells. Endocrinology 137:3461–3468
Stroh T, Jackson AC, Dal Farra C et al (2000) Receptor-mediated internalization of somatostatin in rat cortical and hippocampal neurons. Synapse 38:177–186
Sullivan SJ, Schonbrunn A (1988) Distribution of somatostatin receptors in RINm5F insulinoma cells. Endocrinology 122:1137–1145
Susini C, Buscail L (2006) Rationale for the use of somatostatin analogs as antitumor agents. Ann Oncol 17:1733–1742
Takano K, Yasufuku-Takano J, Teramoto A et al (1997) Gi3 mediates somatostatin-induced activation of an inwardly rectifying K+ current in human growth hormone-secreting adenoma cells. Endocrinology 138:2405–2409
Takeba Y, Suzuki N, Takeno M et al (1997) Modulation of synovial cell function by somatostatin in patients with rheumatoid arthritis. Arthritis Rheum 40:2128–2138
Tallent M, Reisine T (1992) Gi alpha 1 selectively couples somatostatin receptors to adenylyl cyclase in pituitary-derived AtT-20 cells. Mol Pharmacol 41:452–455
Tanjasiri P, Kozbur X, Florsheim WH (1976) Somatostatin in the physiologic feedback control of thyrotropin secretion. Life Sci 19:657–660
Tannenbaum GS, McCarthy GF, Zeitler P et al (1990) Cysteamine-induced enhancement of growth hormone-releasing factor (GRF) immunoreactivity in arcuate neurons: morphological evidence for putative somatostatin/GRF interactions within hypothalamus. Endocrinology 127:2551–2560
Tannenbaum GS, Zhang WH, Lapointe M et al (1998) Growth hormone-releasing hormone neurons in the arcuate nucleus express both Sst1 and Sst2 somatostatin receptor genes. Endocrinology 139:1450–1453
Tannenbaum GS, Turner J, Guo F et al (2001) Homologous upregulation of sst2 somatostatin receptor expression in the rat arcuate nucleus in vivo. Neuroendocrinology 74:33–42
Teijeiro R, Rios R, Costoya JA et al (2002) Activation of human somatostatin receptor 2 promotes apoptosis through a mechanism that is independent from induction of p53. Cell Physiol Biochem 12:31–38
Terrillon S, Bouvier M (2004) Roles of G-protein-coupled receptor dimerization. EMBO Rep 5:30–34
Thangaraju M, Sharma K, Liu D et al (1999) Interdependent regulation of intracellular acidification and SHP-1 in apoptosis. Cancer Res 59:1649–1654
Thapar K, Kovacs KT, Stefaneanu L et al (1997) Antiproliferative effect of the somatostatin analogue octreotide on growth hormone-producing pituitary tumors: results of a multicenter randomized trial. Mayo Clin Proc 72:893–900
Theodoropoulou M, Zhang J, Laupheimer S et al (2006) Octreotide, a somatostatin analogue, mediates its antiproliferative action in pituitary tumor cells by altering phosphatidylinositol 3-kinase signaling and inducing Zac1 expression. Cancer Res 66:1576–1582
Tichomirowa MA, Daly AF, Beckers A (2005) Treatment of pituitary tumors: somatostatin. Endocrine 28:93–100
Tostivint H, Lihrmann I, Bucharles C et al (1996) Occurrence of two somatostatin variants in the frog brain: characterization of the cDNAs, distribution of the mRNAs, and receptor-binding affinities of the peptides. Proc Natl Acad Sci USA 93:12605–12610
Tostivint H, Trabucchi M, Vallarino M et al (2004) Molecular evolution of somatostatin genes. In: Srikant CB (ed) Somatostatin. Kluwer, Norwell
Tran VT, Beal MF, Martin JB (1985) Two types of somatostatin receptors differentiated by cyclic somatostatin analogs. Science 228:492–495
Tsuda K, Sakurai H, Seino Y et al (1981) Somatostatin-like immunoreactivity in human peripheral plasma measured by radioimmunoassay following affinity chromatography. Diabetes 30:471–474
Tulipano G, Bonfanti C, Milani G et al (2001) Differential inhibition of growth hormone secretion by analogs selective for somatostatin receptor subtypes 2 and 5 in human growth-hormone-secreting adenoma cells in vitro. Neuroendocrinology 73:344–351
Tulipano G, Soldi D, Bagnasco M et al (2002) Characterization of new selective somatostatin receptor subtype-2 (sst2) antagonists, BIM-23627 and BIM-23454. Effects of BIM-23627 on GH release in anesthetized male rats after short-term high-dose dexamethasone treatment. Endocrinology 143:1218–1224
Tulipano G, Stumm R, Pfeiffer M et al (2004) Differential beta-arrestin trafficking and endosomal sorting of somatostatin receptor subtypes. J Biol Chem 279:21374–21382
Vale W, Brazeau P, Rivier C et al (1975) Somatostatin. Recent Prog Horm Res 31:365–397
Vale W, Rivier J, Ling N et al (1978) Biologic and immunologic activities and applications of somatostatin analogs. Metabolism 27:1391–1401
Vallejo M (2004) Somatostatin gene structure and regulation. In: Srikant CB (ed) Somatostatin. Kluwer, Norwell, pp 1–16
Van Den Bossche B, D’Haeninck E, De Vos F et al (2004) Oestrogen-mediated regulation of somatostatin receptor expression in human breast cancer cell lines assessed with 99mTc-depreotide. Eur J Nucl Med Mol Imaging 31:1022–1030
Van Essen M, Krenning EP, De Jong M et al (2007) Peptide Receptor Radionuclide Therapy with radiolabelled somatostatin analogues in patients with somatostatin receptor positive tumours. Acta Oncol 46:723–734
Vasquez B, Harris V, Unger RH (1982) Extraction of somatostatin from human plasma on octadecylsilyl silica. J Clin Endocrinol Metab 55:807–809
Vidal C, Rauly I, Zeggari M et al (1994) Up-regulation of somatostatin receptors by epidermal growth factor and gastrin in pancreatic cancer cells. Mol Pharmacol 46:97–104
Viollet C, Bodenant C, Prunotto C et al (1997) Differential expression of multiple somatostatin receptors in the rat cerebellum during development. J Neurochem 68:2263–2272
Visser-Wisselaar HA, Van Uffelen CJ, Van Koetsveld PM et al (1997) 17-beta-estradiol-dependent regulation of somatostatin receptor subtype expression in the 7315b prolactin secreting rat pituitary tumor in vitro and in vivo. Endocrinology 138:1180–1189
Wang HL, Bogen C, Reisine T et al (1989) Somatostatin-14 and somatostatin-28 induce opposite effects on potassium currents in rat neocortical neurons. Proc Natl Acad Sci USA 86:9616–9620
Watt HL, Kharmate G, Kumar U (2008) Biology of somatostatin in breast cancer. Mol Cell Endocrinol 286:251–261
Weckbecker G, Raulf F, Stolz B et al (1993) Somatostatin analogs for diagnosis and treatment of cancer. Pharmacol Ther 60:245–264
Weckbecker G, Briner U, Lewis I et al (2002) SOM230: a new somatostatin peptidomimetic with potent inhibitory effects on the growth hormone/insulin-like growth factor-I axis in rats, primates, and dogs. Endocrinology 143:4123–4130
Weckbecker G, Lewis I, Albert R et al (2003) Opportunities in somatostatin research: biological, chemical and therapeutic aspects. Nat Rev Drug Discov 2:999–1017
Weiss RE, Reddi AH, Nimni ME (1981) Somatostatin can locally inhibit proliferation and differentiation of cartilage and bone precursor cells. Calcif Tissue Int 33:425–430
White RE, Schonbrunn A, Armstrong DL (1991) Somatostatin stimulates Ca(2+)-activated K+ channels through protein dephosphorylation. Nature 351:570–573
White JH, Wise A, Main MJ et al (1998) Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature 396:679–682
Whorton MR, Bokoch MP, Rasmussen SG et al (2007) A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein. Proc Natl Acad Sci USA 104:7682–7687
Whorton MR, Jastrzebska B, Park PS et al (2008) Efficient coupling of transducin to monomeric rhodopsin in a phospholipid bilayer. J Biol Chem 283:4387–4394
Wulbrand U, Wied M, Zofel P et al (1998) Growth factor receptor expression in human gastroenteropancreatic neuroendocrine tumours. Eur J Clin Invest 28:1038–1049
Xidakis C, Mastrodimou N, Notas G et al (2007) RT-PCR and immunocytochemistry studies support the presence of somatostatin, cortistatin and somatostatin receptor subtypes in rat Kupffer cells. Regul Pept 143:76–82
Xu Y, Berelowitz M, Bruno JF (1995) Dexamethasone regulates somatostatin receptor subtype messenger ribonucleic acid expression in rat pituitary GH4C1 cells. Endocrinology 136:5070–5075
Xu Y, Song J, Berelowitz M et al (1996) Estrogen regulates somatostatin receptor subtype 2 messenger ribonucleic acid expression in human breast cancer cells. Endocrinology 137:5634–5640
Yamada Y, Post SR, Wang K et al (1992) Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney. Proc Natl Acad Sci USA 89:251–255
Ye WZ, Mathieu S, Marteau C (1999) Somatostatin inhibits the Na+/H+ exchange activity of rat hepatocytes in short term primary culture. Cell Mol Biol (Noisy-le-grand) 45:1183–1189
Yoshioka K, Saitoh O, Nakata H (2002) Agonist-promoted heteromeric oligomerization between adenosine A(1) and P2Y(1) receptors in living cells. FEBS Lett 523:147–151
Zalatnai A, Timar F (2002) In vitro antiangiogenic effect of sandostatin (octreotide) on the proliferation of the placental vessels. Anticancer Res 22:4225–4227
Zapata PD, Ropero RM, Valencia AM et al (2002) Autocrine regulation of human prostate carcinoma cell proliferation by somatostatin through the modulation of the SH2 domain containing protein tyrosine phosphatase (SHP)-1. J Clin Endocrinol Metab 87:915–926
Zatelli MC, Piccin D, Bottoni A et al (2004) Evidence for differential effects of selective somatostatin receptor subtype agonists on alpha-subunit and chromogranin a secretion and on cell viability in human nonfunctioning pituitary adenomas in vitro. J Clin Endocrinol Metab 89:5181–5188
Zatelli MC, Piccin D, Tagliati F et al (2005a) SRC homology-2-containing protein tyrosine phosphatase-1 restrains cell proliferation in human medullary thyroid carcinoma. Endocrinology 146:2692–2698
Zatelli MC, Piccin D, Tagliati F et al (2005b) Dopamine receptor subtype 2 and somatostatin receptor subtype 5 expression influences somatostatin analogs effects on human somatotroph pituitary adenomas in vitro. J Mol Endocrinol 35:333–341
Zatelli MC, Piccin D, Ambrosio MR et al (2006) Antiproliferative effects of somatostatin analogs in pituitary adenomas. Pituitary 9:27–34
Zhang HJ, Redmon JB, Andresen JM et al (1991) Somatostatin and epinephrine decrease insulin messenger ribonucleic acid in HIT cells through a pertussis toxin-sensitive mechanism. Endocrinology 129:2409–2414
Zhou A, Webb G, Zhu X et al (1999) Proteolytic processing in the secretory pathway. J Biol Chem 274:20745–20748
Zhu Y, Yakel JL (1997) Calcineurin modulates G protein-mediated inhibition of N-type calcium channels in rat sympathetic neurons. J Neurophysiol 78:1161–1165
Zhu LJ, Krempels K, Bardin CW et al (1998) The localization of messenger ribonucleic acids for somatostatin receptors 1, 2, and 3 in rat testis. Endocrinology 139:350–357
Zingg HH, Patel YC (1982) Biosynthesis of immunoreactive somatostatin by hypothalamic neurons in culture. J Clin Invest 70:1101–1109
Acknowledgments
The work cited from the author’s laboratory was supported by grants from the Canadian Institute of Health research (MOP 6196, MOP 74465), Canadian breast cancer Foundation BC/Yukon Chapter, Michael Smith foundation of Health Research and Faculty of Pharmaceutical Sciences.
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Kumar, U., Grant, M. (2009). Somatostatin and Somatostatin Receptors. In: Rehfeld, J., Bundgaard, J. (eds) Cellular Peptide Hormone Synthesis and Secretory Pathways. Results and Problems in Cell Differentiation, vol 50. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2009_29
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