Evaluation of .ALPHA.1-Adrenoceptor Subtypes in Human Hypertrophied Prostate Using (3H)YM617, an .ALPHA.1-Selective Antagonist.

The purpose of this study was to demonstrate the distribution of α1-adrenoceptors in the human hypertrophied prostate with [3H]YM617 (a newly synthesized α1-blocker), and to determine the receptor subtype of [3H]YM617 binding sites by the use of chlorethylclonidine dihydrochloride (CEC). The slices of prostate, removed en bloc in 7 patients with benign prostatic hypertrophy and sectioned vertically to the urethra, were preincubated with or without CEC (10μM). The slices were then incubated with [3H]YM617 (1nM) in the presence or absence of phentolamine (100μM). Specific binding of [3H]YM617 was seen relatively homogeneous, and distributed in the periglandular interstitium (mainly corresponding to smooth muscles) of the prostate. The CEC-pretreated specimens showed a decrease in density of specific binding sites (30.9% mean decrease compared with the CEC non-pretreated specimens on quantitative autoradiogram) (p<0.05), but localization was almost the same as in the CEC non-pretreated specimens. Membrane assay gave similar results. These experiments indicate that ca 70% of α1-adrenoceptor binding sites in the hypertrophied prostate are insensitive to CEC, while ca 30% of that are sensitive to CEC.