Mechanism of action of calcitonin gene-related peptide in inhibiting pancreatic enzyme secretion in rats

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^-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. © 1993.