Somatostatin pp 447-462 | Cite as

Regulation and Actions of Gastrointestinal Somatostatin

  • Gary L. Pittenger
  • Aaron I. Vinik
  • Andrea A. Heldsinger
  • Susan Seino
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 188)


Somatostatin (SS), first isolated from ovine hypothalami (1), is also present in large amounts in the gut in several species including man (2–5), providing the second largest store of tissue SS in the body. In the gut the peptide is found in neural structures in the deep submucosa and muscularis and muscularis mucosae (6), as well as in endocrine cells located in the mucosal layer and the epithelia of gut segments (7, 8). The SS containing nerve terminals are spread diffusely along the gatrointestinal tract; the endocrine cells are found concentrated in the fundus and antrum of the stomach, the pancreas, and spread diffusely throughout the rest of gastrointestinal tract (2, 6, 7). The functional correlate of this distribution has not been established. It does appear that circulating SS originates predominantly from the stomach, which may prove to be the primary source for the systemic hormonal form of the peptide (9). Percutaneous transhepatic venous sampling in humans for estimation of SS-like immunoreactivity (SS-LI) levels reveals the highest concentrations in the gastroepiploic vein and the gastrocolic trunk without a positive gradient in the splenic or mesenteric veins (10). Thus, the stomach is likely to be the major source of circulating SS and it is unlikely that the pancreas, small, or large bowel contribute in any measure.


Endocrine Cell Parietal Cell Gastrin Release High Molecular Weight Form Oxyntic Cell 
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  1. 1.
    Brazeau P, Vale W, Burgus R, Ling N, Butcher M, Rivier J, Guillemin R 1973 Hypothalamic peptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 179: 1779.CrossRefGoogle Scholar
  2. 2.
    Arimura A, Sato H, Dupont A, Nishi N, Schally AV 1975 Somatostatin: abundance of immunoreactive hormone in rat stomach and pancreas. Science 189: 1007.PubMedCrossRefGoogle Scholar
  3. 3.
    Kronheim S, Berelowitz M, Pimstone BL 1976 A radioimmunoassay for growth hormone release-inhibiting hormone: method and quantitative tissue distribution. Clin Endocrinol (Oxf) 5: 619.CrossRefGoogle Scholar
  4. 4.
    McIntosh C, Arnold R, Bothe E, Becker H, Kobberling J, Creutzfeldt W 1979 Gastrointestinal somatostatin: extraction and radioimmunoassay in different species. Gut 19: 655.CrossRefGoogle Scholar
  5. 5.
    Canese MG, Bussolati G 1977 Immuno-electron-cytochemical localization on the somatostatin cells in the human antral mucosa. J Histochem Cytochem 25: 1111.PubMedCrossRefGoogle Scholar
  6. 6.
    Hökfelt T, Elfrin LG, Elde R 1977 Occurrence of somatostatin immuoreactivity in some peripheral sympathetic noradrenergic neurons. Proc Natl Acad Sci (USA) 74: 3587.CrossRefGoogle Scholar
  7. 7.
    Polak JM, Grimelius L, Pearse AGE, Bloom SR 1975 Growth-hormone release inhibiting hormone in gastrointestinal and pancreatic D cells. Lancet 1: 1220.PubMedCrossRefGoogle Scholar
  8. 8.
    Alumets J, Sundler F, Häkanson R 1977 Distribution, ontogeny and ultrastructure of somatostatin immunoreactive cells in the pancreas and gut. Cell Tissue Res 185: 465.PubMedCrossRefGoogle Scholar
  9. 9.
    Vinik AI, Shapiro B, Glaser B, Wagner L 1981 Circulating somatostatin in primates. In: Bloom SR, Polak JM (eds) Gut Hormones. Churchill Livingstone, Edinburgh, p 371.Google Scholar
  10. 10.
    Glaser B, Valtysson G, Fajans SS, Vinik AI, Cho K, Thompson N 1981 Gastrointestinal/pancreatic hormone concentrations in the portal venous system of nine patients with organic hyperinsulinemia. Metabolism 39; 10: 1001.CrossRefGoogle Scholar
  11. 11.
    Larson LI, Golterman H, DeMagistris L, Rehfeld JF, Schwartz TZ 1979 Somatostatin cell processes as pathways for paracrine secretion. Science 205: 1393.CrossRefGoogle Scholar
  12. 12.
    Fujita T, Kobayashi S 1977 Structure and function of gut endocrine cells. Int Rev Cytol (Suppl) 6: 187.Google Scholar
  13. 13.
    Vinik AI, Gaginella TS, O’Dorisio TM 1980 Quantification and characterization of somatostatin-like immunoreactivity in isolated cells, mucosa and muscle of intestine of the rat. Gastroenterology 78: 1285.Google Scholar
  14. 14.
    Vinik AI, Gaginella TS, O’Dorisio TM, Shapiro B, Wagner L 1981 The distribution and characterization of somatostatin-like immunoreactivity in epithelial cells, submucosa, and muscle of the rat stomach and intestine. Endocrinology 109: 1921.PubMedCrossRefGoogle Scholar
  15. 15.
    Warren TG, Shields D 1982 Cell-free biosynthesis of somatostatin precursors: evidence for multiple forms of preprosomatostatin. Proc Natl Acad Sci (USA) 79: 3729.CrossRefGoogle Scholar
  16. 16.
    Gomez S, Morel A, Nicolas P, Cohen P 1983 Regional distribution of the Mr 15,000 somatostatin precursor, somatostatin-28 and somatostatin-14 in the rat brain suggests a differential intracellular processing of the high molecular weight species. Biochem Biophys Res Commun 112: 297.PubMedCrossRefGoogle Scholar
  17. 17.
    Noe BD, Spiess J 1983 Evidence for biosynthesis and differential post-translational proteolytic processing of different (pre)prosomatostatins in pancreatic islets. J Biol Chem 258: 1121.PubMedGoogle Scholar
  18. 18.
    Patel YC, Wheatley T, Ning C 1981 Multiple forms of immunoreactive somatostatin: comparison of distribution in neural and non-neural tissues and portal plasma of the rat. Endocrinology 109: 1943.PubMedCrossRefGoogle Scholar
  19. 19.
    Baskin DG, Ensinck JW 1983 Immunocytochemical evidence that somatostatin-28 is a terminal peptide in rat intestinal mucosa. Diabetes 32 (Suppl 1): 167 (Abstract).Google Scholar
  20. 20.
    Lauber ML, Carnier M, Cohen P 1979 Higher molecular weight forms of immunoreactive somatostatin in mouse hypothalamic extracts: evidence of processing in vitro. Proc Natl Acad Sci (USA) 76: 6004.CrossRefGoogle Scholar
  21. 21.
    Patel YC 1983 A high molecular weight form of somatostatin-28 (1–12)-like immunoreactive substance without somatostatin-14 immunoreactivity in the pancreas, Evidence that somatostatin-14 synthesis can occur independently of somatostatin-23. J Clin Invest 72: 2137.PubMedCrossRefGoogle Scholar
  22. 22.
    Larsson LI 1980 Peptide secretory pathways in the GI tract: cytochemical contributions to regulatory physiology of the gut. Am J Physiol 239: G237.PubMedGoogle Scholar
  23. 23.
    Saffouri B, Weir GC, Bitar KN, Makhlouf GM 1980 Gastrin and somatostatin secretion by perfused rat stomach: functional linkage of antral peptides. Am J Physiol (Gastrointest Liver Physiol) 1: G495.Google Scholar
  24. 24.
    Uvnas-Wallensten K, Efendic S, Johannson C, Sjodin L, Cranwell P 1980 Effect of intraluminal pH on the release of somatostatin and gastrin into antral, bulbar, and ileal pouches of conscious dogs. Acta Physiol Scand 110: 391.PubMedCrossRefGoogle Scholar
  25. 25.
    Alino SF, Garcia D, Uvnas-Mosberg K 1982 Evidence of a cholinergic, pH dependent, vagally mediated release of antral somatostatin. Acta Physiol Scand 515 (Suppl): 21.Google Scholar
  26. 26.
    Aino SF, Garcia D, Uvnas-Mosberg K 1983 On the interaction between intragastric pH and electrical vagal stimulation in causing gastric acid secretion and intraluminal release of gastrin and somatostatin in anesthetized rats. Acta Physiol Scand 117: 491.CrossRefGoogle Scholar
  27. 27.
    Wisen 0, Uvnas-Wallensten K, Efendic S, Johansson C 1980 Release of gastrin and somatostatin into the gastric lumen of healthy subjects and patients with duodenal ulcer and achlorhydria. Acta Physiol Scand 108: 297.PubMedCrossRefGoogle Scholar
  28. 28.
    Fink AS, Hedenbro JL, Vinik AI, Unger RH, Fiddian-Green RG 1980 A reciprocal relationship between the release of immunoreactive gastrin and somatostatin-like immunoreactivity from canine antral mucosa in vitro. Curr Surg 37: 63.PubMedGoogle Scholar
  29. 29.
    Vinik AI, Pittenger G, Wagner L, Fiddian-Green RG 1981 Factors regulating the release of immunoreactive somatostatin from isolated canine antral mucosa. In: Millar RP (ed) Neuropeptides, Biochemical and Physiological Studies. Churchill Livingston, Edinburgh, p 315.Google Scholar
  30. 30.
    Pittenger G, Vinik AI, Fiddian-Green RG, Wagner L 1984 A dual role of calcium in release of somatostatin from canine gastric antral mucosa. Am J Physiol 246 (Endocrinol Metab 9): E361.PubMedGoogle Scholar
  31. 31.
    Fiddian-Green RG, Pittenger G, Kothary P, Vinik AI 1983 Role of calcium in the stimulus-secretion coupling of antral gastrin. release. Endocrinology 112: 753.PubMedCrossRefGoogle Scholar
  32. 32.
    Grodsky GM, Bennett LL 1966 Cation requirements for insulin secretion in the isolated perfused pancreas. Diabetes 15: 910.PubMedGoogle Scholar
  33. 33.
    Gerich JE, Frankel BJ, Fanska R, West L, Forsham PH, Grodsky GM 1974 Calcium dependency of glucagon secretion from the in vitro perfused rat pancreas. Endocrinology 94: 1381.PubMedCrossRefGoogle Scholar
  34. 34.
    McIntosh C, Pederson R, Muller M, Brown J 1981 Autonomic nervous control of the gastric somatostatin secretion from the perfused rat stomach. Life Sci 29: 1477.PubMedCrossRefGoogle Scholar
  35. 35.
    Chiba T, Kadowaki S, Taminato T, Kodama H, Chihara K, Seino Y, Fujita T 1983 Effects of acetylcholine and vagal stimulation of somatostatin and gastrin release from isolated perfused rat stomach. Regul Peptides (Suppl 2 ): S2.CrossRefGoogle Scholar
  36. 36.
    Uvnas-Wallensten K, Efendic S, Roovete A, Johannson C 1980 Decreased release of somatostatin into the portal vein following electrical vagal stimulation in the cat. Acta Physiol Scand 109: 393.PubMedCrossRefGoogle Scholar
  37. 37.
    Koop H, Behrens I, McIntosh CHS, Pederson RA, Arnold R, Creutzfeldt W 1980 Adrenergic modulation of gastric somatostatin release in rats. FEBS Lett 118: 248.PubMedCrossRefGoogle Scholar
  38. 38.
    Goto Y, Berelowitz M, Frohman LA 1981 Effect of catecholamines on somatostatin secretion by isolated perfused rat stomach. Am J Physiol 240: E274.PubMedGoogle Scholar
  39. 39.
    Koop H, Behrens I, Bothe E, Koschwitz, McIntosh CHS, Pederson RA, Arnold R, Creutzfeldt W 1983 Adrenergic control of rat gastric somatostatin and gastrin release. Scand J Gastroenterol 18: 65.PubMedCrossRefGoogle Scholar
  40. 40.
    Takai Y, Kishimoto A, Inoue M, Nishizuka Y 1977 Studies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues, I. Purification and characterization of an active enzyme from bovine cerebellum. J Biol Chem 252: 7603.Google Scholar
  41. 41.
    Feyrter F 1983 Uber die peripheren endocrinen (parakrinen), Drusen des Menschen Vienna/Dusseldorf, Verlag, Mandinch, p 27.Google Scholar
  42. 42.
    Vinik AI 1978 Regulation of gastrin release from oriented sheets of human antral mucosa in vitro. In Bloom SR (ed) Gut Hormones. Churchill Livingstone, Edinburgh, p 156.Google Scholar
  43. 43.
    Fiddian-Green RG, Pittenger G, Kothary P, Vinik AI 1980 Effect of luminal somatostatin on acid secretion and gastrin release. Scand J Gastroenterol 15: 305.PubMedCrossRefGoogle Scholar
  44. 44.
    Gomez-Pan A, Reed JD, Albinus M, Shaw B, Hall R, Besser GM, Coy DH, Kastin AJ, Schally AV 1975 Direct inhibition of gastric acid and pepsin secretion by growth-hormone release-inhibiting hormone in cats. Lancet 1: 888.PubMedCrossRefGoogle Scholar
  45. 45.
    Takemura J, Seino Y, Nishi S, Ishida H, Sakita M, Taminato T, Chiba T, Imura H 1983 Effects of prostaglandin E2 and D2 on gastric somatostatin and gastrin secretion. Regul Peptides 6: 379.CrossRefGoogle Scholar
  46. 46.
    Reyl F, Lewin MJM 1981 Somatostatin is a potent activator of phosphoprotein phosphatase in the digestive tract. Biochem Biophys Acta 675: 297.PubMedCrossRefGoogle Scholar
  47. 47.
    LeRoith D, Vinik AI, Epstein S, Baron P, Olkenitzky MN, Pimstone BL 1985 Somatostatin and serum gastrin in normal subjects and in patients with pernicious anemia, chronic liver disease and renal disease. S Afr Med J 49: 1601.Google Scholar
  48. 48.
    Barros D’Sa AA, Bloom SR, Baron JH 1975 Direct inhibition of gastric acid secretion by growth-hormone release-inhibiting hormone in dogs. Lancet 1: 886.CrossRefGoogle Scholar
  49. 49.
    Hansson HPJ 1967 Histochemical demonstration of carbonic anhydrase. Hitochemie 11: 112.CrossRefGoogle Scholar
  50. 50.
    Heldsinger AA, Vinik AI 1984 Action of gastrin in guinea pig oxyntic cells. Studies using quantification cytochemistry. J Clin Invest 74: 124.Google Scholar
  51. 51.
    Klaff LJ, Vinik AI, Heldsinger AA 1981 Comparison of potency of acid secretagogues in the activation of carbonic anhydrase (CA) in guinea pig parietal cells. In: Millar RP (ed) Neuropeptides, Biochemical and Physiologic Studies. Churchill Livingstone, Edinburgh, 35: 336.Google Scholar
  52. 52.
    Walker W, Vinik AI, Heldsinger AA, Kaveh R 1983 The role of calcium and calmodulin in activation of the oxyntic cell by histamine and carbamylcholine in the guinea pig. J Clin Invest 72: 955.PubMedCrossRefGoogle Scholar
  53. 53.
    Vinik AI, Heldsinger AA 1984 Cytochemical quantification of physiologic regulation of oxyntic cell carbonic anhydrase. Ann NY Acad Sci 429: 592.PubMedCrossRefGoogle Scholar
  54. 54.
    Vinik AI, Heldsinger A, Skoglund ML 1983 Evidence for histamine H1 and H2 receptors in guinea pig oxyntic cells. J Pharmacol Exp Ther 22: 115.Google Scholar
  55. 55.
    Vinik AI, Shapiro B, Pienta K, Heldsinger A 1981 Somatostatin is an agonist and noncompetitive antagonist of gastrin in oxyntic cell function. Endocrinology 109: 1117.PubMedCrossRefGoogle Scholar
  56. 56.
    Theoharides T, Douglas WW 1978 Somatostatin induces histamine secretion from rat peritoneal mast cells. Endocrinology 102: 1637.PubMedCrossRefGoogle Scholar
  57. 57.
    Lingunsky M, Goto Y, Debas H, Yamada T 1983 Prostaglandins mediate inhibition of gastric acid by somatostatin in the rat. Science 219: 301.CrossRefGoogle Scholar
  58. 58.
    Curry DL, Bennett LL 1974 Reversal of somatostatin inhibition of insulin secretion by calcium. Biochem Biophys Res Commun 60: 1015.PubMedCrossRefGoogle Scholar
  59. 59.
    Scholz D, Schwille P 1978 Somatostatin and intestinal calcium absorption in man. Metabolism 27 (Suppl 1): 1349.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • Gary L. Pittenger
    • 1
  • Aaron I. Vinik
    • 1
  • Andrea A. Heldsinger
    • 1
  • Susan Seino
    • 1
  1. 1.Department of Surgery and Internal MedicineUniversity of Michigan Medical SchoolAnn ArborUSA

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