CALCITONIN-GENE-RELATED PEPTIDE-I PREFERENTIALLY STIMULATES SECRETIONOF SOMATOSTATIN FROM INTESTINAL CULTURES

Calcitonin gene-related peptide (CGRP)-I has been reported to inhibit gastric acid secretion through stimulation of gastric somatostatin-14 (S-14) release. To establish whether some of the effects of CGRP-I on intestinal function might also be mediated through somatostatin, fetal rat intestinal cultures were treated with test agents for 2 h, and th e secretion of somatostatin-like immunoreactive (SLI) peptides was det ermined by RIA. The intestinal cultures have been previously found to synthesize and secrete both major forms of intestinal somatostatin (S- 28 and S-14). Rat (r) CGRP-I treatment of the intestinal cultures stim ulated SLI secretion to 163 +/- 33% of the control level at 3.3 x 10(- 7) m (P < 0.01) and 227 +/- 30% of the control level at 10(-6) M (P < 0.001). In contrast, the structurally related peptide, human CGRP-II, had no effect on total SLI release at any concentration up to 10(-6) M . Gel permeation chromatography revealed that rCGRP-1 increased the se cretion of S-14 by 22 +/- 6-fold (P < 0.01) compared to the control va lue, whereas that of S-28 increased nonsignificantly by only 2 +/- 1-f old. Thus, the ratio of S-28 to S-14 secreted into the medium decrease d from 1.7 +/- 0.2 in control medium to 0.2 +/- 0.3 after rCGRP-I trea tment (P < 0.01). As the ratio of S-28 to S-14 stored by the cells was not altered by rCGRP-1 treatment, these findings suggest that intesti nal S-28 and S-14 may be secreted by two distinct intestinal D-cells w ith different sensitivities to rCGRP-I or by a single D-cell type cont aining distinct pools of S-14 and S-28 that have different sensitiviti es to rCGRP-I. The results of these in vitro studies further indicate that in vivo, CGRP-I may modulate aspects of intestinal function throu gh its stimulation of the secretion of S-14.