The alpha‐adrenoceptor subtype mediating the tension of human prostatic smooth muscle

We have characterized the α 1 adrenoceptor subtypes in the human prostate using radioligand receptor binding studies. The objective of the present study was to determine the α 1 subtype mediating the tension of prostatic smooth muscle. Fresh human tissue was obtained from 9 males between 50 and 80 years of age undergoing prostatectomy for BPH. The incubation of prostatic tissue with the irreversible antagonist chlorethyclonidine (CEC) resulted in an 80% reduction of the maximal contractile response produced by phenylephrine. However, the α 1A ‐selective antagonists WB‐4101 and 5‐methylurapidil (5‐MU) competitively inhibited the contractile response induced by phenylephrine, with K B = 2.64 and 4.46 nM, respectively, consistent with their affinity at the α A1 receptor subtype. The pharmacological profile of the α 1 ‐receptor‐mediated contractile response of prostate smooth muscle is inconsistent with their classification as either an α 1A or α 1B subtype. Alternatively, when compared with the properties of the cloned α 1 receptors, our results suggest that the α 1 receptors involved in the contraction of prostate smooth muscle have some pharmacological properties similar to those encoded by the gene of the bovine α 1c receptor subtype. The findings of the present study suggest that efforts should be made to confirm the identity of the α 1 ‐receptor subtype expressed by prostate smooth muscle, in order to develop subtype‐selective α 1 antagonists, and to evaluate their safety and efficacy in benign prostatic hyperplasia (BPH). © 1993 Wiiey‐Liss, inc.