title: Mechanism of action of calcitonin gene-related peptide in inhibiting pancreatic enzyme secretion in rats.
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.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: F
authors.initials: F
authors.lastname: Kolligs
authors.forename: C
authors.initials: C
authors.lastname: Owyang
mesh_terms: 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
chemical_list: D001626:Bethanechol Compounds; D011506:Proteins; D018723:Bethanechol; D003847:Deoxyglucose; D015740:Calcitonin Gene-Related Peptide; D012844:Sincalide