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

Abstract

We have characterized the α₁ adrenoceptor subtypes in the human prostate using radioligand receptor binding studies. The objective of the present study was to determine the α₁ 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 α₁-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 α₁ receptors, our results suggest that the α₁ 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 α₁-receptor subtype expressed by prostate smooth muscle, in order to develop subtype-selective α₁ antagonists, and to evaluate their safety and efficacy in benign prostatic hyperplasia (BPH). © 1993 Wiiey-Liss, inc.