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 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.
Li
Y
Y
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
Kolligs
F
F
Owyang
C
C
D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology; D004558:Electric Stimulation; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology
D001626:Bethanechol Compounds; D011506:Proteins; D018723:Bethanechol; D003847:Deoxyglucose; D015740:Calcitonin Gene-Related Peptide; D012844:Sincalide