Prosomatostatin 1–64 Is a Major Product of Somatostatin Gene Expression in Pancreas and Gut

Abstract

Prosomatostatin (pro-SS) is a peptide of 92 amino acids which contains the extensively studied somatostatin (SS) 1-28 and SS 1-14 at the C terminus. Little is known about the N-terminal part of pro-SS. In previous studies, using a radioimmunoassay against pro-SS 20-36 (sequence deduced from human cDNA sequence) we have identified a peptide with a molecular mass of approximately 8000 daltons in extracts of pancreas and intestinal mucosa. Using a variety of chromatographic procedures we have now isolated this peptide from extracts of pancreas and intestinal mucosa from pigs. The isolated peptides were sequenced on an Applied Biosystems gas phase sequenator and cleaved with the Asp-N endopeptidase for sequencing of C-terminal fragments. The peptides had an amino acid sequence identical to human pro-SS 1-64. In effluent from isolated perfused preparations of porcine small intestine and pancreas we identified upon appropriate stimulation pro-SS 20-36 immunoreactive peptides that by isocratic high pressure liquid chromatography appeared identical to pro-SS 1-64. An identical peptide was identified in pig plasma. Thus, in pancreas and gut pro-SS processing gives rise to the same pro-SS 1-64 molecule in spite of differential processing of the C terminus (SS 1-14 in pancreas and SS 1-28 in gut). The eventual hormonal role of pro-SS 1-64 may now be evaluated.