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Endocrinology, Vol 133, 2833-2837, Copyright © 1993 by Endocrine Society
ARTICLES |
PL Brubaker and GR Greenberg
Department of Physiology, University of Toronto, Ontario, Canada.
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 the secretion of somatostatin-like immunoreactive (SLI) peptides was determined 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 stimulated 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-I increased the secretion of S-14 by 22 +/- 6-fold (P < 0.01) compared to the control value, whereas that of S-28 increased nonsignificantly by only 2 +/- 1- fold. Thus, the ratio of S-28 to S-14 secreted into the medium decreased from 1.7 +/- 0.2 in control medium to 0.2 +/- 0.3 after rCGRP- I treatment (P < 0.01). As the ratio of S-28 to S-14 stored by the cells was not altered by rCGRP-I treatment, these findings suggest that intestinal S-28 and S-14 may be secreted by two distinct intestinal D- cells with different sensitivities to rCGRP-I or by a single D-cell type containing distinct pools of S-14 and S-28 that have different sensitivities to rCGRP-I. The results of these in vitro studies further indicate that in vivo, CGRP-I may modulate aspects of intestinal function through its stimulation of the secretion of S-14.
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P. L. Brubaker, K. A. Gronau, S. L. Asa, and G. R. Greenberg Nutrient and Peptide Regulation of Somatostatin-28 Secretion from Intestinal Cultures Endocrinology, January 1, 1998; 139(1): 148 - 155. [Abstract] [Full Text] [PDF] |
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