Central CGRP inhibits pancreatic enzyme secretion by modulation of vagal parasympathetic outflow

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Original languageEnglish
Journal / PublicationAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number5 38-5
Publication statusPublished - 1998
Externally publishedYes


Calcitonin gene-related peptide (CGRP) is a potent inhibitor of pancreatic enzyme secretion in vivo. Recent studies have shown that CGRP exerts its inhibitory action at a central vagal site. The present study investigates the mechanism responsible for the central action of CGRP. Rats were fitted with lateral cerebro-ventricular cannulas, using stereotaxic instruments, 4 days before pancreatic secretion studies. In anesthetized rats, administration of 2-deoxy-D-glucose (2-DG) (75 mg/kg iv) or CCK-8 (40 pmol·kg-1·h-1) produced a 100 and 75% increase in protein secretion, respectively, which was completely blocked by atropine. Intracerebroventricular (ICV) administration of CGRP (0.03-0.6 nmol/h) resulted in a dose-related inhibition of pancreatic protein secretion evoked by 2-DG or CCK-8. CGRP administered by the ICV route was 10-40 times more potent than CGRP given by the intravenous route. In contrast, ICV administration of CGRP had no significant effect on pancreatic protein secretion evoked by electrical vagal stimulation or bethanechol, which directly activates the pancreatic muscarinic receptor. Chemical sympathectomy induced by pretreatment with guanethedine (20 mg/kg ip, 2 days) or α- adrenergic receptor blockade with phentolamine did not alter the inhibitory effects of CGRP. We recently demonstrated that CCK stimulated the enteropancreatic neural pathways to mediate pancreatic secretion in rats with a chronic vagotomy. ICV-administered CGRP did not affect CCK-stimulated pancreatic secretion in rats with a chronic vagotomy. In conclusion, CGRP in the central nervous system inhibits pancreatic enzyme secretion stimulated by 2-DG and CCK-8, which act through vagal pathways. The inhibitory action of CGRP is not mediated by the sympathetic nervous system but appears to depend on intact vagus nerves.

Research Area(s)

  • Calcitonin gene-related peptide, Cholecystokinin, Chronic vagotomy, Sympathetic nervous system, Vagal pathways