Pharmacologic characterization of cloned α₁-adrenoceptor subtypes: selective antagonists suggest the existence of a fourth subtype

In membranes prepared from Cos-7 or HeLa cells expressing one of three individual cloned α₁-adrenoceptor subtypes, competition with 2-{(β-(4-hydroxy-3-[¹²⁵I]iodophenyl)ethylaminomethyl}-tetralone ([¹²⁵I]HEAT) by the selective compounds [+] niguldipine, 5-methyl-urapidil and benoxathian reveals high affinity for the clones α₁-adrenoceptor subtype and low affinity for both the cloned α_1A-adrenoceptor and α_1B-adrenoceptor. Competition with [¹²⁵I]HEAT by spiperone revealed high affinity for the cloned α_1C-adrenoceptor, intermediate affinity for the cloned α_1B-adrenoceptor, and low affinity for the cloned α_1A-adrenoceptor. Combining pharmacological properties previously described for α₁-adrenoceptor subtypes in rat membranes and here described from cloned receptors, these data suggest the existence of a fourth distinct α₁-adrenoceptor subtype.