Brubaker P L, Greenberg G R
Department of Physiology, University of Toronto, Ontario, Canada.
Endocrinology. 1993 Dec;133(6):2833-7. doi: 10.1210/endo.133.6.7902270.
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.
据报道，降钙素基因相关肽（CGRP）-I可通过刺激胃生长抑素-14（S-14）释放来抑制胃酸分泌。为确定CGRP-I对肠道功能的某些作用是否也可能通过生长抑素介导，将胎鼠肠道培养物用受试药物处理2小时，并用放射免疫分析法测定生长抑素样免疫反应性（SLI）肽的分泌。先前已发现肠道培养物能合成并分泌两种主要形式的肠道生长抑素（S-28和S-14）。用大鼠（r）CGRP-I处理肠道培养物，在3.3×10⁻⁷M时刺激SLI分泌至对照水平的163±33%（P<0.01），在10⁻⁶M时刺激至对照水平的227±30%（P<0.001）。相比之下，结构相关肽人CGRP-II在高达10⁻⁶M的任何浓度下对总SLI释放均无影响。凝胶渗透色谱显示，与对照值相比，rCGRP-I使S-14的分泌增加了22±6倍（P<0.01），而S-28仅非显著增加了2±1倍。因此，分泌到培养基中的S-28与S-14的比例从对照培养基中的1.7±0.2降至rCGRP-I处理后的0.2±0.3（P<0.01）。由于rCGRP-I处理未改变细胞储存的S-28与S-14的比例，这些发现表明肠道S-28和S-14可能由对rCGRP-I敏感性不同的两种不同肠道D细胞分泌，或者由含有对rCGRP-I敏感性不同的不同S-14和S-28池的单一D细胞类型分泌。这些体外研究结果进一步表明，在体内，CGRP-I可能通过刺激S-14分泌来调节肠道功能的某些方面。
