Digestive motor effects and vascular actions of CGRP in dog are expressed by different receptor subtypes.
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.
L'Heureux
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MC
CHUM, Saint-Luc, Université de Montréal, Centre de recherche, 264 East Rene-Levesque Blvd., Montreal, Canada.
St-Pierre
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Trudel
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Plourde
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Lepage
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Poitras
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D004285:Dogs; D004386:Duodenum / Q000502:physiology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology; D019518:Postprandial Period; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000187:drug effects / Q000502:physiology*; D013270:Stomach / Q000502:physiology
D010446:Peptide Fragments; D018015:Receptors, Calcitonin Gene-Related Peptide; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide