Peptides derived from cleavage of prosomatostatin at carboxyl- and amino-terminal segments. Characterization of tissue and secreted forms in the rat.

Tissue and secreted forms of rat prosomatostatin and its cleavage products were characterized immunochemically using high performance liquid chromatography and sequence-specific radioimmunoassays directed against somatostatin-14 (S-14), S-28-(1-12), and S-28-(1-14). Acetic or hydrochloric acid extracts of hypothalamus, pancreas, stomach, and jejunum contained seven molecular forms of Mr = 10,400 (corresponding to prosomatostatin (pro-S], Mr = 6,800 (7-kDa peptide, consisting of an NH2-terminally truncated form of pro-S), Mr = 7,600 (8-kDa peptide, corresponding to pro-S-(1-76), i.e. pro-S minus the COOH-terminal -Arg-Lys-S-14), Mr = 5,600 (5-kDa peptide, corresponding to pro-S-(33-76)) and three peptides co-chromatographing with synthetic S-14, S-28, and S-28-(1-12). Acid/ethanol extracts of these tissues contained pro-S, 8-kDa peptide, S-28, S-14, and S-28-(1-12) forms, but not the 7- and 5-kDa species. Pepstatin inhibited 7- and 5-kDa peptide formation in acetic acid extracts of tissues. The secreted forms consisted of the same five forms present in acid/ethanol or acetic acid plus pepstatin tissue extracts. The 7- and 5-kDa peptides were not secreted and appeared to be derived artifactually, presumably through the action of renin- and cathepsin D-like acid proteases. Accurate quantitation of the 8-kDa peptide by acid/ethanol extraction revealed a variable tissue distribution. Since the presence of the 8-kDa form provides evidence for direct processing of pro-S----S-14 + 8-kDa peptide, the present data suggest that pro-S----S-14 conversion is important for S-14 synthesis in the hypothalamus and pancreas, tissues rich in the 8-kDa form, but not in the stomach and jejunal mucosa, which contain low concentrations of this peptide.