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  • Title: Mechanism of action of calcitonin gene-related peptide in inhibiting pancreatic enzyme secretion in rats.
    Author: Li Y, Kolligs F, Owyang C.
    Journal: Gastroenterology; 1993 Jul; 105(1):194-201. PubMed ID: 8099887.
    Abstract:
    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 micrograms.kg-1 x h-1. Similarly, CGRP at a dose of 50 micrograms.kg-1 x h-1 completely 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.
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