Receptor Subtypes Involved in the α₁-Adrenoceptor Mediated Increase in ⁸⁶Rb⁺ Efflux from the Rat Heart

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The aim of this study was to determine the involvement of the different α₁-adrenoceptor subtypes in the α₁-adrenoceptor mediated increase in ⁸⁶Rb⁺ efflux from rat hearts. Isolated hearts were perfused in the presence of a, β-adrenoceptor antagonist (1 μM timolol). After loading with ⁸⁶Rb⁺, the efflux was measured during α1-adrenoceptor stimulation by phenylephrine (30μM). Phenylephrine increased the ⁸⁶Rb⁺ efflux by about 30%. Pretreatment with the preferentially α_1B-adrenoceptor inhibitor chloroethylclonidine (CEC), reduced the response to phenylephrine by about 50%. The preferential α_1D-adrenoceptor inhibitor BMY 7378 inhibited the response to phenylephrine by 35%, with a pK_I=8.4 (95% C.I. 8.2-8.6). The response was sensitive to the preferential α_1A-adrenoceptor inhibitors (+)niguldipine, 5-methylurapidil (5-MU) and WB-4101 at relatively high concentrations, and 5-MU inhibited the response with a pKI = 7.7 (95% C.I. 7.2-8.0) in CEC pretreated hearts. In conclusion, the phenylephrine stimulated increase in ⁸⁶Rb⁺ efflux in the rat heart is not specifically linked to only one of the α₁-adrenoceptor subtypes, but involves the α_1B and the α_1D-adrenoceptor subtypes, and probably the α_1A-adrenoceptor subtype as well.