RECEPTOR SUBTYPES INVOLVED IN THE ALPHA(1)-ADRENOCEPTOR MEDIATED INCREASE IN RB-86(-HEART() EFFLUX FROM THE RAT)

The aim of this study was to determine the involvement of the differen t alpha(1)-adrenoceptor subtypes in the alpha(1)-adrenoceptor mediated increase in Rb-86(+) efflux from rat hearts. Isolated hearts were per fused in the presence of a beta-adrenoceptor antagonist (1 mu M timolo l). After loading with Rb-86(+), the eft-lux was measured during alpha (1)-adrenoceptor stimulation by phenylephrine (30 mu M). Phenylephrine increased the Rb-86(+) efflux by about 30%. Pretreatment with the pre ferentially alpha(1B)-adrenoceptor inhibitor chloroethyl-clonidine (CE C), reduced the response to phenylephrine by about 50%. The preferenti al alpha(1D)-adrenoceptor inhibitor BMY 7378 inhibited the response to phenylephrine by 35%, with a pK(1)=8.4 (95% C.I. 8.2-8.6). The respon se was sensitive to the preferential alpha(1A)-adrenoceptor inhibitors (+)niguldipine, 5-methylurapidil (5-MU) and WE-4101 at relatively hig h concentrations, and 5-MU inhibited the response with a pK(1)=7.7 (95 % C.I. 7.2-8.0) in CEC pretreated hearts. In conclusion, the-phenyleph rine stimulated increase in Rb-86(+) efflux in the rat heart is not sp ecifically linked to only one of the al-adrenoceptor subtypes, but inv olves the alpha(1B)- and the alpha(1D)-adrenoceptor subtypes, and prob ably the alpha(1A)-adrenoceptor subtype as well.