Radioligand binding studies of α1‐adrenoceptor subtypes in rat heart

Open Access
Publisher Website
Google Scholar
Abstract
1 In order to characterize the α1-adrenoceptor subtypes mediating positive inotropic effects of adrenaline (in the presence of propranolol) in rat right ventricular strips and the Ca2+ sources used to elicit them, we have used radioligand binding to identify the α1-adrenoceptor subtypes present in rat heart and the α1-adrenoceptor affinity and subtype-selectivity of various pharmacological tools. 2 Amitryptiline, mianserin, trimipramine, oxaprotiline, clonidine, chloroethylclonidine, phenoxybenzamine, BE 2254 and 8-OH-DPAT competed for [3H]-prazosin binding in rat heart, vas deferens, liver, spleen, cerebral cortex and hippocampus but none of them displayed detectable α1-adrenoceptor subtype-selectivity; nitrendipine did not compete for [3H]-prazosin binding in concentrations up to ***5 μmoll−1. 3 The α1A-adrenoceptor-selective, 5-methyl-urapidil, (+)-niguldipine, and to a lesser extent (–)-niguldipine competed for [3H]-prazosin binding in rat heart, vas deferens, cerebral cortex and hippocampus with shallow and biphasic curves; analysis of these curves demonstrated that rat heart contains α1A- and α1B-adrenoceptors in a 20:80 ratio. 4 Treatment of rat right ventricular strips with 100 μmoll−1 chloroethylclonidine for 30 min at 30°C followed by 60 min washout reduced the number of α1-adrenoceptors, as assessed by [3H]-prazosin saturation experiments, by 74%. Treatment with 100 μmol 1−1 CdCl2 did not affect number or affinity of cardiac α1-adrenoceptors and combined treatment with chloroethylclonidine and CdCl2 reduced α1-adrenoceptor number by 90%. 5 Treatment of rat right ventricular strips with chloroethylclonidine steepened 5-methyl-urapidil competition curves and increased the relative contribution of α1A-adrenoceptors from 26 to 89%. Treatment with CdCl2 did not affect 5-methyl-urapidil competition curves and combined treatment with chloroethylclonidine and CdCl2 increased the relative contribution of α1A-adrenoceptors to 66%. 6 We conclude that rat heart contains α1A- and α1B-adrenoceptors in a 20:80% ratio. Treatment with chloroethylclonidine reduces α1B-adrenoceptor number by 96% but has only minor effects on α1A-adrenoceptor density. Treatment with CdCl2 does not affect the number of either α1-adrenoceptor subtype.

This publication has 22 references indexed in Scilit: