EVALUATION OF ALPHA-(1)-ADRENOCEPTOR SUBTYPES IN HUMAN HYPERTROPHIED PROSTATE USING [H-3] YM617, AN ALPHA-(1)-SELECTIVE ANTAGONIST

The purpose of this study was to demonstrate the distribution of alpha (1)-adrenoceptors in the human hypertrophied prostate with [H-3]YM617 (a newly synthesized al-blocker), and to determine the receptor subtyp e of [H-3]YM617 binding sites by the use of chlorethylclonidine dihydr ochloride (CEC). The slices of prostate, removed en bloc in 7 patients with benign prostatic hypertrophy and sectioned vertically to the ure thra, were preincubated with or without CEC (10 mu M). The slices were then incubated with [H-3] YM617 (1 nM) in the presence or absence of phentolamine (100 mu M). Specific binding of [H-3]YM617 was seen relat ively homogeneous, and distributed in the periglandular interstitium ( mainly corresponding to smooth muscles) of the prostate. The CEC-pretr eated specimens showed a decrease in density of specific binding sites (30.9% mean decrease compared with the CEC non-pretreated specimens o n quantitative autoradiogram) (p<0.05), but localization was almost th e same as in the CEC non-pretreated specimens. Membrane assay gave sim ilar results. These experiments indicate that ca 70% of ar-adrenocepto r binding sites in the hypertrophied prostate are insensitive to CEC, while ca 30% of that are sensitive to CEC.