Identification of alpha 1-adrenoceptor subtypes in rat lung by binding of [3H]-prazosin and [3H]-WB4101.

The alpha 1-adrenoceptor subtypes in rat lung were characterized according to their binding of [3H]-prazosin or [3H]-WB4101 and were compared with that in rat liver. [3H]-prazosin bound with high affinity to an apparently homogeneous population of sites in rat lung. The binding of [3H]-prazosin was inhibited by WB4101, benoxathian and 5-methylurapidil biphasically but the proportions differed between WB4101 or benoxathian and 5-methylurapidil. In the lung membranes pretreated with chloroethylclonidine a single population with high affinity for WB4101 and benoxathian was detected while 5-methylurapidil still discriminated two sites of distinctly different affinities. These results suggest that the WB4101-high affinity sites of rat lung were subdivided further into two subclasses according to 5-methylurapidil binding affinity. In fact, [3H]-WB4101 bound to lung membranes with two different affinities and the high affinity binding sites were subdivided by 5-methylurapidil into two classes. By contrast, [3H]-prazosin or [3H]-WB4101 binding sites of liver membranes were detected as a single population with high affinity for prazosin but with low affinity for WB4101, benoxathian and 5-methylurapidil. These results suggest that the alpha 1-adrenoceptors of rat lung are composed of three distinct subtypes (alpha 1A, alpha 1B and unknown subtypes) while that of liver is of alpha 1B subtype. Two radioligands with different affinities may be used as powerful probes to identify receptor subclasses.