High-affinity specific [³H]tamsulosin binding to α₁ in human prostates with benign prostatic hypertrophy

Abstract

The binding of a novel radioligand, [³H]tamsulosin, to human prostatic membranes with benign prostatic hypertrophy (BPH) has been characterized. [³H]Tamsulosin rapidly associated with its binding sites in human prostatic membranes with BPH, and the binding reached steady state by 30 min at 25°C. The rate constants for association and dissociation of [³H]tamsulosin binding were calculated to be 0.21±0.05/nM per minute and 0.01±0.004/min, respectively. The specific binding of [³H]tamsulosin in human prostatic membranes was saturable and of high affinity (K _d=0.04±0.01 nM). The density of [³H]tamsulosin-binding sites (B _max) was 409±28 fmol/mg protein. The K _d and B _max values for [³H]tamsulosin binding in human prostates were significantly lower than those for [³H]prazosin binding. [³H]tamsulosin binding was remarkable for its significantly lower degree of nonspecific binding. Six α-adrenoceptor antagonists competed with [³H]tamsulosin for the binding sites in the rank order: tamsulosin>WB4101>prazosin>S-(+)-isomer>naftopidil>yohimbine. The binding affinities (pK_i) of these antagonists for [³H]tamsulosin binding in human prostates closely correlated with their pharmacological potencies (pA₂) in prostates. In conclusion, [³H]tamsulosin selectively labels α₁-adrenoceptors in human prostates, and thus may become a useful radioligand for the further analysis of these receptors.