THE ALPHA-ADRENOCEPTOR SUBTYPE MEDIATING THE TENSION OF HUMAN PROSTATIC SMOOTH-MUSCLE

We have characterized the alpha1 adrenoceptor subtypes in the human prostate using radioligand receptor binding studies. The objective of the present study was to determine the alpha1-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 alpha1A-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 alpha1A receptor subtype. The pharmacological profile of the alpha1-receptor-mediated contractile response of prostate smooth muscle is inconsistent with their classification as either an alpha1A or alpha1B subtype. Alternatively, when compared with the properties of the cloned alpha1 receptors, our results suggest that the alpha1 receptors involved in the contraction of prostate smooth muscle have some pharmacological properties similar to those encoded by the gene of the bovine alpha1C receptor subtype. The findings of the present study suggest that efforts should be made to confirm the identity of the alpha1-receptor subtype expressed by prostate smooth muscle, in order to develop subtype-selective alpha1 antagonists, and to evaluate their safety and efficacy in benign prostatic hyperplasia (BPH). (C) 1993 Wiley-Liss, Inc.