Effects of MDL 72222 and methiothepin on carotid vascular responses to 5-hydroxytryptamine in the pig: Evidence for the presence of ?5-hydroxytryptamine1-like? receptors

Abstract

The present study concerns the effects of MDL 72222 (0.5 mg · kg⁻¹, i.v.), a 5-hydroxytryptamine₃ (5-HT₃) receptor antagonist, and methiothepin (1.0 mg · kg⁻¹, i.v.), an antagonist of both 5-HT₂ and “5-HT₁-like” receptors, on the responses to local infusions of 5-HT (2.0 μg · kg⁻¹ · min⁻¹) on the total common carotid artery blood flow and its complete distribution in anaesthetized pigs. As reported earlier, more than 80% of the carotid blood bypassed the capillary circulation via cranial arteriovenous anastomoses, while approximately 15% and 2% was distributed to the extracerebral structures and brain, respectively. The total carotid blood flow did not change or was moderately reduced by 5-HT, but the amine consistently caused a 85% reduction in arteriovenous anastomotic blood flow and a 5-fold increase in blood flow to the extracerebral tissues, mainly the skin and ears. The colour of the skin and ears changed to bright pink. Complete recovery from the effects of 5-HT was observed once the infusion was stopped. MDL 72222 and methiothepin did not themselves affect carotid haemodynamics. The responses to 5-HT were not modified by MDL 72222 except that the reduction of the total carotid blood flow by 5-HT was augmented. In contrast, methiothepin almost completely abolished both the reduction of arteriovenous anastomotic blood flow and the increase in tissue blood flow following 5-HT-infusion. The colour of the skin and ears also did not become pink. In conjunction with our earlier findings that the constriction of arteriovenous anastomoses and the dilatation of arterioles caused by 5-HT within the carotid territory of the pig are not attenuated by 5-HT₂ receptor antagonists (cyproheptadine, methysergide, ketanserin and WAL 1307), and are mimicked by agonists at “5-HT₁-like” receptors (5-carboxamidotryptamine and BEA 1654), our results clearly establish that these responses are mediated by “5-HT₁-like” receptors.