Somatostatin pp 89-107 | Cite as

Somatostatin-28 [1–12] — Like Peptides

  • R. Benoit
  • P. Bohlen
  • N. Ling
  • F. Esch
  • A. Baird
  • S. Y. Ying
  • W. B. Wehrenberg
  • R. Guillemin
  • J. H. Morrison
  • C. Bakhit
  • L. Koda
  • F. E. Bloom
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 188)


The search for a peptide corresponding to the NH2-terminus of somatostatin-28 (SS-28) in tissues has led to the isolation and characterization of somatostatin-28[1–12] from pancreas and hypothalamus. Somatostatin-28[1–12]-like immunoreactivity [SS-28[1–12]-LI] is widely distributed throughout the central nervous sytem and the digestive system of rodents and primates, reaching levels comparable to those of somatostatin-14 (SS-14). Antibodies directed against the C-terminal end of the dodecapeptide are more specific and constitute excellent markers for the “prosomatostatin” system in mammalian tissues. In rat brain, SS-28[1–12]-LI material is highly concentrated in nerve fibres and terminals, especially in the median eminence, layer I of neocortex, the outer molecular layer of the dentate gyrus and the striatum. Additionally, immunoreactivity is observed in large multipolar or occasionally pyramidal-like neurons of the neocortex. SS-28[1–12] is secreted from hypothalamus and amygdala by a calcium dependent mechanism. No biological role is presently known for the dodecapeptide.

Two other peptides of Mr = 8000 (8K) and Mr = 5000 (5K) which contain SS-28[1–12] at their carboxy-termini are present in acid extracts from rat pancreas, brain and spinal cord. These two peptides were isolated from an acid extract of rat brains using ion-exchange chromatography, gel permeation chromatography and reverse-phase HPLC. Results from amino acid analysis and partial sequencing were compared to the sequence of the cDNA encoding rat pre-prosoma-tostatin (prepro-SS) and revealed that the 8K peptide is a 76 amino acid molecule corresponding to prepro-SS[25–100] and that the 5K peptide, which contains 44 amino acids, corresponds to prepro-SS [57–100]. The 5K peptide was generated after cleavage of a Leu-Leu bond at position 56–57 of prepro-SS. The four most predominant peptides of the “prosomatostatin system” presently characterized are: SS-14, SS-28[1–12], SS-28 and prepro-SS[25–100]. Studies on pooled perfusates from rat hypothalamic tissue show that prepro-SS [25–100] is released with SS-28[1–12] in vitro and accounts for 22% of the total SS-28[1–12]-like immunoreactive material released during depolarization. The 5K peptide is apparently not secreted.

The presence of prepro-SS[25–100] in brain implies that, first, prosomatostatin can serve as an immediate precursor for SS-14 without going through SS-28 as an intermediate step and second, other peptides could conceivably be derived from the cryptic portion of the precursor.


Median Eminence Immunoreactive Material Antibody Population Outer Molecular Layer Immune Plasma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Pradayrol L, Jørnvall H, Mutt V, Ribet A 1980 N-terminally extended somatostatin: the primary structure of somatostatin-28. FEBS Lett 109:55.Google Scholar
  2. 2.
    Brazeau P, Vale W, Burgus R, Ling N, Butcher M, Rivier J, Guillemin R 1973 Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 179: 77.PubMedCrossRefGoogle Scholar
  3. 3.
    Schally AV, Huang W-Y, Chang RCC, Arimura A, Redding TW, Millar RP, Hunkapiller MW, Hood LE 1980 Isolation and structure of pro-somatostatin: a putative somatostatin precursor from pig hypothalamus. Proc Natl Acad Sci (USA) 77: 4489.CrossRefGoogle Scholar
  4. 4.
    Esch F, Böhlen P, Ling N, Benoit R, Brazeau P, Guillemin R 1980 Primary structure of ovine hypothalamic somatostatin-28 and somatostatin-25. Proc Natl Acad Sci (USA) 77: 6827.CrossRefGoogle Scholar
  5. 5.
    Spiess J, Villareal J, Vale W 1981 Isolation and sequence analysis of a somatostatin-like polypeptide from ovine hypothalamus. Biochemistry 20: 1982–1988.PubMedCrossRefGoogle Scholar
  6. 6.
    Böhlen P, Brazeau P, Esch F, Ling N, Guillemin R 1981 Isolation and chemical characterization of somatostatin-28 from rat hypothalamus. Regulatory Peptides 2: 359.PubMedCrossRefGoogle Scholar
  7. 7.
    Brazeau P, Ling N, Esch F, Böhlen P, Benoit R, Guillemin R 1981 High biological activity of the synthetic replicates of somatostatin-28 and somatostatin-25. Reguatory Peptides 1: 255.CrossRefGoogle Scholar
  8. 8.
    Rodriguez-Arnao MD, Rainbow SJ, Comaru-Schally AM, Meyners CA, Gomez-Pan A, Woodhead S, Schally AV, Coy DH, Hall R 1981 Effects of prosomatostatin on growth hormone and prolactin response to arginine in man. Comparison with somatostatin. Lancet 14: 353.Google Scholar
  9. 9.
    Meyers CA, Murphy WA, Redding TW, Coy DH, Schally AV 1980 Synthesis and biological actions of prosomatostatin. Proc Natl Acad Sci (USA) 77: 6171.CrossRefGoogle Scholar
  10. 10.
    Mandarino L, Stenner D, Blanchard W, Nissen S, Gerich J, Ling N, Brazeau P, Böhlen P, Esch F, Guillemin R 1981 Selective effects of somatostatin-14,-25 and -28 on in vitro insulin and glucagon secretion. Nature 291: 76.PubMedCrossRefGoogle Scholar
  11. 11.
    Brown M, Rivier J, Vale W 1981 Somatostatin-28: selective action on the pancreatic B-cell and brain. Endocrinology 108: 2391.PubMedCrossRefGoogle Scholar
  12. 12.
    Pradayrol LL, Bommelaer G, Fourmy D, Fagot-Recurat P, Rozental G, Essaid A, Bousson M, Wunsch E, Ribet A 1982 Inhibition de la libération de l’hormone de croissance chez l’homme: effets comparés des somatostatines-14 et -28. Gastroenterol Clin Biol 6: 166.PubMedGoogle Scholar
  13. 13.
    Vaysse N, Pradayrol L, Chayvialle JA, Pignal F, Esteve JP, Susini F, Descos F, Ribet A 1981 Effects of somatostatin-14 and somatostatin-28 on bombesin stimulated release of gastrin, insulin and glucagon in the dog. Endocrinology 108: 1843.PubMedCrossRefGoogle Scholar
  14. 14.
    Benoit R, Böhlen P, Ling N, Briskin A, Esch F, Brazeau P, Ying S-Y, Guillemin R 1982 Presence of somatoatin-28(1–12) in hypothalamus and pancreas. Proc Natl Acad Sci (USA) 79: 917.CrossRefGoogle Scholar
  15. 15.
    Benoit R, Bohlen P, Ling N, Brazeau P, Shibasaki T, Guillemin R, A somatostatin-28-like peptide in rat medullary thyroid carcinoma. Program of the 65th annual meeting of the Fed Amer Soc Exper Biol, Atlanta, GA 1981, p 457 (abstract 1289 ).Google Scholar
  16. 16.
    Ravazzola M, Benoit R, Ling N, Guillemin R, Orci L 1983 Immuno- cytochemical localization of prosomatostatin fragments in maturing and mature secretory granules of pancreatic and gastrointestinal D-cells. Proc Natl Acad Sci (USA) 80: 215.CrossRefGoogle Scholar
  17. 17.
    Benoit R, Ling N, Alford B, Guillemin R 1982 Seven peptides derived from prosomatostatin in rat brain. Biochem Biophys Res Commun 107: 944.PubMedCrossRefGoogle Scholar
  18. 18.
    Morrison JH, Benoit R, Magistretti PJ, Ling N, Bloom FE 1982 Immunohistochemical distribution of pro-somatostatin related peptides in the hippocampus. Neurosci Lett 34: 137.PubMedCrossRefGoogle Scholar
  19. 19.
    Morrison JH, Benoit R, Magistretti PJ, Bloom FE 1983 Immunohistochemical distribution of pro-somatostatin related peptides in cerebral cortex. Brain Res 262: 344.PubMedCrossRefGoogle Scholar
  20. 20.
    Iversen LL, Iversen SD, Bloom F, Douglas C, Brown M, Vale W 1978 Calcium-dependent release of somatostatin and neurotensin from rat brain in vitro. Nature (Lond.) 273: 161.CrossRefGoogle Scholar
  21. 21.
    Kewley CF, Millar RP, Berman MC, Schally AV 1981 Depolariation and ionophore-induced release of octacosa somatostatin from stalk median eminence synapotosomes. Science 213: 913.PubMedCrossRefGoogle Scholar
  22. 22.
    Peterfreund RA, Vale W 1982 High molecular weight somatostatin secretion by cultured rat brain cells. Brain Res 239: 463.PubMedCrossRefGoogle Scholar
  23. 23.
    Bakhit C, Benoit R, Bloom FE 1983 Release of somatostatin-28(1–12) from hypothalamus in vitro. Nature (Lond.) 301: 524.CrossRefGoogle Scholar
  24. 24.
    Sheward WJ, Benoit R, Fink G 1984 Somatostatin-28[1–12] is secreted into hypophysial portal vessel blood in the rat. Neuroendocrinology 38: 88.PubMedCrossRefGoogle Scholar
  25. 25.
    Bloom FE, Aldenhoff J, Bakhit C, Benoit R, French E, Gruol D, Koda L, Morrison J, Siggins G, Gut peptides in the brain: implications for therapeutics. In Ilnd World Conference on Clinical Pharmacology and Therapeutics. Symposium on Neuropeptides, Washington, 1983.Google Scholar
  26. 26.
    Benoit R, Ling N, Bakhit C, Morrison JH, Alford B, Guillemin R 1982 Somatostatin-28 1–12 -like immunoreactivity in the rat. Endocrinology 111: 2149.PubMedCrossRefGoogle Scholar
  27. 27.
    Benoit R, Böhlen P, Esch F, Ling N 1984 Neuropeptides derived from prosomatostatin that do not contain the somatostatin-14 sequence. Brain Res 311: 23.PubMedCrossRefGoogle Scholar
  28. 28.
    Esch F 1984 Polypeptide microsequence analysis with the commercially available gas-phase sequencer. Anal Biochem 136: 39.PubMedCrossRefGoogle Scholar
  29. 29.
    Goodman RH, Aron DC, Roos BA 1983 Rat pre-prosomatostatin. Structure and processing by microsomal membranes. J Biol Chem 258: 5570.PubMedGoogle Scholar
  30. 30.
    Shen L-P, Pictet RL, Rutter WJ 1982 Human somatostatin I: sequence of the cDNA. Proc Natl Acad Sci (USA) 79: 4575.CrossRefGoogle Scholar
  31. 31.
    Funckes CL, Ninth CD, Deschenes R, Magazin M, Tavianini MA, Sheets M, Collier K, Weith HL, Aron DC, Roos BA, Dixon JE 1983 Cloning and characterization of a mRNA-encoding rat preprosomatostatin. J Biol Chem 258: 8781.PubMedGoogle Scholar
  32. 32.
    Patzelt C, Tager HS, Carroll RJ, Steiner DF 1980 Identification of prosomatostatin in pancreatic islets. Proc Natl Acad Sci (USA) 77: 2410.CrossRefGoogle Scholar
  33. 33.
    Spiess J, Vale W 1980 Multiple forms of somatostatin-like activity in the rat hypothalamus. Biochemistry 19: 2861.PubMedCrossRefGoogle Scholar
  34. 34.
    Zingg HH, Patel YC 1982 Processing of synthetic somatostatin28 and a related endogenous rat hypothalamic somatostatin-like molecule to somatostatin-14 by hypothalamic enzymes. Life Sci 30: 525.PubMedCrossRefGoogle Scholar
  35. 35.
    Sagar SM, Landry D, Millard WJ, Badger TM, Arnold MA, Martin JB 1982 Depletion of somatostatin-like immunoreactivity in the rat central nervous sytem by cysteamine. J Neurosci 2: 225.PubMedGoogle Scholar
  36. 36.
    Ackland J, Ratter S, Bourne GL, Rees LH 1983 Characterization of immunoreactive somatostatin in human fetal hypothalamic tissue. Regulatory Peptides 5: 95.PubMedCrossRefGoogle Scholar
  37. 37.
    Bakhit C, Koda L, Benoit R, Morrison JH, Bloom FE 1984 Evidence for selective release of somatostatin-14 and somatostatin28[1–12] from rat hypothalamus. J Neurosci 4: 411.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • R. Benoit
    • 1
  • P. Bohlen
    • 1
  • N. Ling
    • 1
  • F. Esch
    • 1
  • A. Baird
    • 1
  • S. Y. Ying
    • 1
  • W. B. Wehrenberg
    • 1
  • R. Guillemin
    • 1
  • J. H. Morrison
    • 2
  • C. Bakhit
    • 2
  • L. Koda
    • 2
  • F. E. Bloom
    • 2
  1. 1.Laboratories for NeuroendocrinologyUSA
  2. 2.A.V. Davis Center for Behavioral NeurobiologyThe Salk InstituteSan DiegoUSA

Personalised recommendations