We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Native profiles of alpha(1A)-adrenoceptor phenotypes in rabbit prostate.
- Authors
Su, T.-H.; Morishima, S.; Suzuki, F.; Yoshiki, H.; Anisuzzaman, A. S. M.; Tanaka, T.; Cheng, J.-T.; Muramatsu, I.
- Abstract
Background and purpose:α1-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 α1-adrenoceptor phenotypes and to clarify their relationship.Experimental approach:Binding experiments with [3H]-silodosin and [3H]-prazosin were performed using intact tissue segments and crude membrane preparations of rabbit prostate and the results were compared with α1-adrenoceptor-mediated prostate contraction.Key results:[3H]-Silodosin at subnanomolar concentrations bound specifically to intact tissue segments of rabbit prostate. However, [3H]-prazosin at the same range of concentrations failed to bind to α1-adrenoceptors of intact segments. Binding sites of [3H]-silodosin in intact segments were composed of α1L phenotype with low affinities for prazosin (pKi=7.1), 5-methyurapidil and N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-α,α-dimethyl-1H-indole-3-ethamine hydrochloride (RS-17053), and α1A-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 α1-adrenoceptors in the membrane preparations at the same density with a subnanomolar affinity, showing a typical profile of ‘classical’ α1A-adrenoceptors (pKi for prazosin=9.8). The pharmacological profile of α1-adrenoceptor-mediated prostate contraction was in accord with the α1L phenotype observed by intact segment binding approach.Conclusions and implications:Three distinct phenotypes (α1L and α1A-like phenotypes in the intact segments and a classical α1A phenotype in the membranes) with different affinities for prazosin were detected in rabbit prostate. It appears that the three phenotypes are phenotypic subtypes of α1A-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
- Subjects
PHENOTYPES; ADRENERGIC receptors; PHARMACOLOGY; LIGAND binding (Biochemistry); LABORATORY rabbits
- Publication
British Journal of Pharmacology, 2008, Vol 155, Issue 6, p906
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1038/bjp.2008.318