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

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 (30 μM). Phenylephrine increased the 86Rb+ efflux by about 30%. Pretreatment with the preferentially α1b-adrenoceptor inhibitor chloroethyl-clonidine (CEC), reduced the response to phenylephrine by about 50%. The preferential α1d-adrenoceptor inhibitor BMY 7378 inhibited the response to phenylephrine by 35%, with a pKi = 8.4 (95% C.I. 8.2–8.6). The response was sensitive to the preferential α1a-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 α1b- and the α1d-adrenoceptor subtypes, and probably the α1a-adrenoceptor subtype as well.