Alpha-1 adrenoceptors in human prostate: characterization and alteration in benign prostatic hypertrophy.

Alpha-1 adrenoceptors in hypertrophied prostates of humans were characterized by a binding assay using [3H]prazosin as a radioligand. Specific [3H]prazosin binding in hypertrophied prostates of humans was saturable and of high affinity (Kd = 0.6 nM) with a maximal number of binding sites of 106 fmol/mg of protein, and it showed a pharmacological specificity as well as stereo-selectivity which characterized alpha-1 adrenoceptors. Adrenergic antagonists competed for the binding in order: R-(-)-YM-12617(5-[2-[[2-(o-ethoxyphenoxy)ethyl]amino]propyl]-2- methoxybenzenesulfonamide HCl) greater than (+/-)-YM-12617 = prazosin greater than phentolamine greater than S-(+)-YM-12617 greater than idazoxan. R-(-)- and (+/-)-YM-12617, alpha-1 adrenoceptor antagonists, have been shown to exhibit an extremely high affinity for prostatic [3H]prazosin binding sites (Ki = 0.6 and 1.1 nM, respectively). In addition, R-(-)-YM-12617 was approximately 100 times as potent as the S-(+)-isomer. The affinities of prazosin and YM-12617 compounds for [3H]prazosin binding sites in hypertrophied prostates of humans correlated closely with their pharmacological potencies in prostates reported previously. The blockade of [3H]prazosin binding sites in hypertrophied prostates of humans induced by (+/-)-YM-12617 was easily reversed by washing. There was a significant 35% increase in the maximal number of binding sites for [3H] prazosin binding in hypertrophied prostates from benign prostatic hypertrophy compared to normal tissues, whereas the hypertrophy had little effect on the Kd value.(ABSTRACT TRUNCATED AT 250 WORDS)