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 bloo d vessels and nerves of the GI tract. Activation of CGRP receptors (subtype s 1 or 2) usually induces vasodilation and/or muscle relaxation, but its ef fects in dog and on gastroduodenal motility are still unclear. This study l ooked for the effect of CGRP and the antagonist CGRP8-37, specific for CGRP type 1 receptor, 1) on GT 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 m odify the duration of the migrating motor complex nor the release nor the m otor action of plasma motilin. The gastric emptying of a solid meal (15 g m eat/kg) was reduced by the administration of CGRP1-37 (AUC: 2196 +/- 288.6 versus 3618 +/- 288.4 with saline or T1/2: 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 bas al 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 co uld influence digestive motility by slowing the gastric emptying of a meal through an action on CGRP-I receptors. Hemodynamic effects of CGRP were not blocked by CGRP8-37 and seem therefore mediated by CGRP-2 receptor subtype . (C) 2000 Elsevier Science Inc. All rights reserved.