ALPHA1 ADRENOCEPTOR SUBTYPES IN THE HUMAN PROSTATE

High affinity alpha1 adrenoceptors have been characterized in the human prostate. The tension of prostatic smooth muscle is mediated by the al adrenoceptor. The present study represents the first characterization of human al adrenoceptor subtypes using radioligand receptor binding techniques. Binding studies were performed on tissue homogenates obtained from the human prostate. Competitive inhibition studies were performed in the presence of an 80 pM. I-125-Heat and 16 concentrations of unlabelled 5-methylurapidil (5 MU) or WB-4101 (10(-10) M. to 10(-5) M.). Saturation experiments were also performed with and without chloroethylclonidine (CEC, 10(-5) M.), a compound that selectively inactivates the alpha1B subtype. The individual displacement plots for WB-4101 and 5-MU in the human prostate were consistently best fit by a 2 binding site model. WB-4101 and 5-MU exhibited a 594- and 186-fold higher affinity for the prostatic alpha1A binding site relative to the alpha1B binding site. The ratios of prostatic alpha1A/alpha1B binding sites discriminated by WB-4101 and 5-MU were 1.8 and 1.6, respectively. CEC inactivated 44% of the prostatic alpha1 binding sites. The binding studies suggest that the dominant alpha1 subtype in the human prostate is the alpha1A. We are characterizing the functional properties of the alpha1 subtypes in the human prostate.