5-HT4-like receptors in mammalian atria

Abstract

Atrial myocardium of man and pig possess receptors that mediate positive inotropic effects and/or positive chronotropic effects of 5-hydroxytryptamine (5-HT). These 5-HT receptors are blocked with moderate affinity (pKB = 6.7-6.9) by 3 alpha-trophanyl-1H-indole-3-carboxylate (ICS 205930) but not by antagonists of alpha- and beta-adrenoceptors, or 5-HT1 subtypes, 5-HT2 and 5-HT3 receptors. In human and porcine atrium the receptors also mediate 5-HT-induced increases of both cyclic AMP levels and cyclic AMP-dependent protein kinase activity. Human and porcine atrial 5-HT receptors are also partially activated by the benzamides renzapride and cisapride albeit with lower potency and efficacy than 5-HT. The properties of these atrial 5-HT receptors resemble those of "so called" 5-HT4 receptors, positively coupled to the adenylyl cyclase of mouse embyonic colliculi neurons. However, for colliculi 5-HT4 receptors the benzamides have greater efficacy and ICS 205930 lower affinity than for atrial 5-HT receptors. The atrial 5-HT receptors of man and pig are, therefore, designated 5-HT4-like receptors. Guinea-pig night atria appear to have a mixture of 5-HT3- and 5-HT4-like receptors involved in the mediation of positive chronotropic effects of 5-HT.