Digestive motor effects and vascular actions of CGRP in dog are expressed by different receptor subtypes

Peptides. 2000 Mar;21(3):425-30. doi: 10.1016/s0196-9781(00)00160-1.

Abstract

Calcitonin gene-related peptide (CGRP) is a 37 AA peptide localized in blood vessels and nerves of the GI tract. Activation of CGRP receptors (subtypes 1 or 2) usually induces vasodilation and/or muscle relaxation, but its effects in dog and on gastroduodenal motility are still unclear. This study looked for the effect of CGRP and the antagonist CGRP8-37, specific for CGRP type 1 receptor, 1) on GI motility (interdigestive and postprandial), and 2) on hemodynamy, in conscious dogs. During the interdigestive period, the infusion of CGRP1-37 (200 pmol/kg/h) or CGRP8-37 (2000 pmol/kg/h) did not modify the duration of the migrating motor complex nor the release nor the motor action of plasma motilin. The gastric emptying of a solid meal (15 g meat/kg) was reduced by the administration of CGRP1-37 (AUC: 2196 +/- 288.6 versus 3618 +/- 288.4 with saline or T12: 78 +/- 7.3 versus 50 +/- 4.3 min; P < 0.01) and this effect was reversed by the antagonist CGRP8-37. CGRP1-37 significantly (P < 0. 01) diminished arterial pressures (118 +/- 1.6/64 +/- 1.4 vs. 125 +/- 1.4/75 +/- 1.2 mmHg with saline) and accelerated the basal cardiac rhythm (110 +/- 1.4 versus 83 +/- 1.6 beats/min). However, CGRP8-37 failed to block the cardiovascular effects of CGRP1-37. In dog, CGRP could influence digestive motility by slowing the gastric emptying of a meal through an action on CGRP-1 receptors. Hemodynamic effects of CGRP were not blocked by CGRP8-37 and seem therefore mediated by CGRP-2 receptor subtype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Calcitonin Gene-Related Peptide / pharmacology*
  • Dogs
  • Duodenum / physiology
  • Female
  • Gastrointestinal Motility / drug effects*
  • Gastrointestinal Motility / physiology
  • Heart Rate / drug effects
  • Hemodynamics / drug effects*
  • Hemodynamics / physiology
  • Humans
  • Peptide Fragments / pharmacology
  • Postprandial Period
  • Receptors, Calcitonin Gene-Related Peptide / drug effects
  • Receptors, Calcitonin Gene-Related Peptide / physiology*
  • Stomach / physiology

Substances

  • Peptide Fragments
  • Receptors, Calcitonin Gene-Related Peptide
  • calcitonin gene-related peptide (8-37)
  • Calcitonin Gene-Related Peptide