Native profiles of α 1A ‐adrenoceptor phenotypes in rabbit prostate

Background and purpose: α 1 ‐Adrenoceptors in the rabbit prostate have been studied because of their controversial pharmacological profiles in functional and radioligand binding studies. The purpose of the present study is to determine the native profiles of α 1 ‐adrenoceptor phenotypes and to clarify their relationship. Experimental approach: Binding experiments with [ 3 H]‐silodosin and [ 3 H]‐prazosin were performed using intact tissue segments and crude membrane preparations of rabbit prostate and the results were compared with α 1 ‐adrenoceptor‐mediated prostate contraction. Key results: [ 3 H]‐Silodosin at subnanomolar concentrations bound specifically to intact tissue segments of rabbit prostate. However, [ 3 H]‐prazosin at the same range of concentrations failed to bind to α 1 ‐adrenoceptors of intact segments. Binding sites of [ 3 H]‐silodosin in intact segments were composed of α 1L phenotype with low affinities for prazosin (pKi=7.1), 5‐methyurapidil and N ‐[2‐(2‐cyclopropylmethoxyphenoxy)ethyl]‐5‐chloro‐α,α‐dimethyl‐1 H ‐indole‐3‐ethamine hydrochloride (RS‐17053), and α 1A ‐like phenotype with moderate affinity for prazosin (pKi=8.8) but high affinity for 5‐methyurapidil and RS‐17053. In contrast, both radioligands bound to a single population of α 1 ‐adrenoceptors in the membrane preparations at the same density with a subnanomolar affinity, showing a typical profile of ‘classical’ α 1A ‐adrenoceptors (pKi for prazosin=9.8). The pharmacological profile of α 1 ‐adrenoceptor‐mediated prostate contraction was in accord with the α 1L phenotype observed by intact segment binding approach. Conclusions and implications: Three distinct phenotypes (α 1L and α 1A ‐like phenotypes in the intact segments and a classical α 1A phenotype in the membranes) with different affinities for prazosin were detected in rabbit prostate. It appears that the three phenotypes are phenotypic subtypes of α 1A ‐adrenoceptors, but are not genetically different subtypes. British Journal of Pharmacology (2008) 155 , 906–912; doi: 10.1038/bjp.2008.318 ; published online 11 August 2008