Somatostatin-28 [1-12]-like peptides.

R. Benoit, P. Bohlen, N. Ling, F. Esch, A. Baird, S. Y. Ying, W. B. Wehrenberg, R. Guillemin, John Morrison, C. Bakhit

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Abstract

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 system 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 (8 K) and Mr = 5000 (5 K) 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-prosomatostatin (prepro-SS) and revealed that the 8 K 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 5 K 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 5 K 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.

Original languageEnglish (US)
Pages (from-to)89-107
Number of pages19
JournalAdvances in Experimental Medicine and Biology
Volume188
StatePublished - Jan 1 1985
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Benoit, R., Bohlen, P., Ling, N., Esch, F., Baird, A., Ying, S. Y., Wehrenberg, W. B., Guillemin, R., Morrison, J., & Bakhit, C. (1985). Somatostatin-28 [1-12]-like peptides. Advances in Experimental Medicine and Biology, 188, 89-107.