Mechanism of action of calcitonin gene-related peptide in inhibiting pancreatic enzyme secretion in rats.
Mechanism of action of calcitonin gene-related peptide in inhibiting pancreatic enzyme secretion in rats.
复制标题
降钙素基因相关肽抑制大鼠胰酶分泌的作用机制。
DOI：
10.1016/0016-5085(93)90026-9
复制
发表时间：
1993
期刊：
影响因子：
29.4
通讯作者：
Owyang,C
中科院分区：
文献类型：
--
作者：
Li,Y;Kolligs,F;Owyang,C
背景：近年来，降钙素基因相关肽(CGRP)受体已被发现存在于中枢神经系统。方法：用大鼠进行体内实验，观察CGRP对中枢迷走神经刺激剂2-脱氧-d-葡萄糖(2DG)、生理条件下经迷走神经传入通路作用的胆囊素、电刺激迷走神经刺激胰腺的乙酰胆碱释放、直接激活胰腺M受体的胆碱能神经刺激所引起的胰酶分泌的影响。2 5μg·kg−1·h−1可完全抑制胰腺蛋白质分泌。同样，5 0μg·kg−1·h−1可完全抑制生理浓度八肽缩胆囊素(CCK 8)所致的胰腺蛋白分泌。相反，由苯二酚或电刺激迷走神经干引起的胰腺蛋白分泌不受CGRP的影响。迷走神经周围应用辣椒素可抑制CCK-8诱导的胰腺反应，但不影响2DG诱导的胰腺反应，排除了CGRP对迷走神经传入通路的影响。结论：CGRP通过迷走神经通路抑制CCK-8或CCK-8诱导的胰酶分泌。CGRP在迷走神经中央部位发挥抑制作用。
Background:Recently, calcitonin gene-related peptide (CGRP) receptors have been identified in the central nervous system. Therefore whether CGRP inhibits pancreatic enzyme secretion at a central site was investigated.Methods:In vivo studies were performed on rats to examine the effect of CGRP on pancreatic enzyme secretion evoked by stimulants that act on different sites: (1) 2-Deoxy-d-glucose (2DG), a central vagal stimulant; (2) cholecystokinin, which acts via vagal afferent pathways under physiologic conditions; (3) electric vagal nerve stimulation, which stimulates vagal release of acetylcholine in the pancreas; and (4) bethanechol, which directly activates pancreatic muscarinic receptors.Results:CGRP produced a dose related inhibition of pancreatic secretion evoked by 2DG. Complete inhibition was observed at a dose of 25 μg · kg−1· h−1. Similarly, CGRP at a dose of 50 μg · kg−1· h−1completely inhibited pancreatic protein secretion in response to a physiological concentration of cholecystokinin octapeptide (CCK-8). In contrast, pancreatic protein secretion evoked by bethanechol or electrical stimulation of the vagal trunk were unaffected by CGRP. It was also shown that perivagal capsaicin treatment impaired pancreatic responses to CCK-8 but not to 2DG ruling out an effect of CGRP on vagal afferent pathway.Conclusions:Our data indicates that CGRP inhibits pancreatic enzyme secretion evoked by 2DG or CCK-8 via vagal pathways. CGRP exerts its inhibitory action at a central vagal site.