High-affinity specific [3H]tamsulosin binding to ?1 in human prostates with benign prostatic hypertrophy

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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 (pKi) 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.