IDENTIFICATION OF ALPHA(1)-ADRENOCEPTOR SUBTYPES IN RAT LUNG BY BINDING OF [H-3] PRAZOSIN AND [H-3] WB4101

The alpha(1)-adrenoceptor subtypes in rat lung were characterized acco rding to their binding of [H-3]-prazosin or [H-3]-WB4101 and were comp ared with that in rat liver. [H-3]-prazosin bound with high affinity t o an apparently homogeneous population of sites in rat lung. The bindi ng of [H-3]-prazosin was inhibited by WB4101, benoxathian and 5-methyl urapidil biphasically but the proportions differed between WB4101 or b enoxathian and 5-methylurapidil. In the lung membranes pretreated with chloroethylclonidine a single population with high affinity for WB410 1 and benoxathian was detected while 5-methylurapidil still discrimina ted two sites of distinctly different affinities. These results sugges t that the WB4101-high affinity sites of rat lung were subdivided furt her into two subclasses according to 5-methylurapidil binding affinity . In fact, [H-3]-WB4101 bound to lung membranes with two different aff inities and the high affinity binding sites were subdivided by 5-methy lurapidil into two classes. By contrast, [H-3]-prazosin or [H-3]-WB410 1 binding sites of liver membranes were detected as a single populatio n with high affinity for prazosin but with low affinity for WB4101, be noxathian and 5-methylurapidil. These results suggest that the alpha(1 )-adrenoceptors of rat lung are composed of three distinct subtypes (a lpha(1A), alpha(1B) and unknown subtypes) while that of liver is of al pha(1B) subtype. Two radioligands with different affinities may be use d as powerful probes to identify receptor subclasses.