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

Abstract

We have characterized the alpha 1 adrenoceptor subtypes in the human prostate using radioligand receptor binding studies. The objective of the present study was to determine the alpha 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 alpha 1A-selective antagonists WB-4101 and 5-methylurapidil (5-MU) competitively inhibited the contractile response induced by phenylephrine, with KB = 2.64 and 4.46 nM, respectively, consistent with their affinity at the alpha 1A receptor subtype. The pharmacological profile of the alpha 1-receptor-mediated contractile response of prostate smooth muscle is inconsistent with their classification as either an alpha 1A or alpha 1B subtype. Alternatively, when compared with the properties of the cloned alpha 1 receptors, our results suggest that the alpha 1 receptors involved in the contraction of prostate smooth muscle have some pharmacological properties similar to those encoded by the gene of the bovine alpha 1C receptor subtype. The findings of the present study suggest that efforts should be made to confirm the identity of the alpha 1-receptor subtype expressed by prostate smooth muscle, in order to develop subtype-selective alpha 1 antagonists, and to evaluate their safety and efficacy in benign prostatic hyperplasia (BPH).