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

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2000-03, Vol.21 (3), p.425-430
• Main Authors: L’Heureux, Marie-Claude, St-Pierre, Serge, Trudel, Louise, Plourde, Victor, Lepage, Raymond, Poitras, Pierre
• Format: Article
• Language: English
• Subjects: Animals; Blood Pressure - drug effects; Calcitonin Gene-Related Peptide - pharmacology; Dogs; Duodenum - physiology; Female; Gastric emptying; Gastroduodenal motility; Gastrointestinal Motility - drug effects; Gastrointestinal Motility - physiology; Heart Rate - drug effects; Hemodynamics - drug effects; Hemodynamics - physiology; Humans; Migrating motor complex; Motilin; Peptide Fragments - pharmacology; Postprandial Period; Receptors, Calcitonin Gene-Related Peptide - drug effects; Receptors, Calcitonin Gene-Related Peptide - physiology; Regulatory peptides; Stomach - physiology
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/S0196-9781(00)00160-1

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 T 1 2 : 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.