COMPARATIVE-STUDY ON ALPHA(1)-ADRENOCEPTOR ANTAGONIST BINDING IN HUMAN PROSTATE AND AORTA

1. Specific binding of [H-3]-prazosin in prostatic and aortic membranes of humans was saturable and of high affinity (prostate: apparent dissociation constant, Kd = 0.35 +/- 0.03 nmol/ L; aorta: Kd = 0.26 +/- 0.03 nmol/L). The density of [H-3]-prazosin binding sites (B-max) for prostate and aorta was 546 +/- 31 and 61.6 +/- 1.6 fmol/mg protein, respectively. 2. Prazosin, YM617, naftopidil and urapidil competed with [H-3]-prazosin for the binding sites in a dose-dependent manner in the prostate and aorta of humans. The binding affinities of these antagonists in both tissues were compared, based on the inhibition constant, K-i. Both prazosin and urapidil showed similar affinity to [H-3]-prazosin binding sites in human tissue, whereas YM617 and naftopidil showed approximately a 12 and two times higher affinity, respectively, to alpha(1)-adrenoceptor sites of prostate than aorta. 3. The chloroethylclonidine treatment reduced partially the B-max values for specific [H-3]-prazosin binding in the prostate and aorta of humans with little effect on the K-d values. 4. These data suggest that YM617 is a relatively selective antagonist of human prostatic alpha(1)-adrenoceptors.