Native profiles of α_1A‐adrenoceptor phenotypes in rabbit prostate

Abstract

Background and purpose: a 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 a 1 -adrenoceptor phenotypes and to clarify their relationship. 3 H]-silodosin in intact segments were composed of a 1L phenotype with low affinities for prazosin (pKi ¼ 7.1), 5-methyurapidil and N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-a,a-dimethyl-1H-indole-3-ethamine hydrochloride (RS-17053), and a 1A -like phenotype with moderate affinity for prazosin (pKi ¼ 8.8) but high affinity for 5-methyurapidil and RS-17053. In contrast, both radioligands bound to a single population of a 1 -adrenoceptors in the membrane preparations at the same density with a subnanomolar affinity, showing a typical profile of 'classical' a 1A -adrenoceptors (pKi for prazosin ¼ 9.8).The pharmacological profile of a 1 -adrenoceptor-mediated prostate contraction was in accord with the a 1L phenotype observed by intact segment binding approach. Conclusions and implications: Three distinct phenotypes (a 1L and a 1A -like phenotypes in the intact segments and a classical a 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 a 1A -adrenoceptors, but are not genetically different subtypes.

Phenotype pharmacology of lower urinary tract α1‐adrenoceptors

“…3 H]-prazosin at subnanomolar concentrations cannot bind sufficiently to a1L-adrenoceptors (Su et al, 2008;Muramatsu et al, 2009). Silodosin and its tritiated radioligand are known to be of equally high affinity for both the a1A-and a1L-adrenoceptors Su et al, 2008) (Table 2).…”

“…Silodosin and its tritiated radioligand are known to be of equally high affinity for both the a1A-and a1L-adrenoceptors Su et al, 2008) (Table 2).…”

Influence of Tissue Integrity on Pharmacological Phenotypes of Muscarinic Acetylcholine Receptors in the Rat Cerebral Cortex

“…A binding assay that uses intact tissue segments has been shown to be a powerful method for analysis of the intrinsic properties of receptors present in native tissues (Muramatsu et al, 2005Anisuzzaman et al, 2008a;Sathi et al, 2008;Su et al, 2008). When using the intact segment binding assay, in contrast to conventional membrane binding assays, it is not necessary to consider either the change of receptor characteristics that may occur upon tissue homogenization that eliminates the receptor's natural environment or the selective loss of receptors upon isolating membranes by differential centrifugation (Muramatsu et al, 2005).…”

Evaluation of β1L-Adrenoceptors in Rabbit Heart by Tissue Segment Binding Assay

“…These lines of evidence suggest that the pharmacological profile of β 1L -adrenoceptor can not be interpreted by a simple conformational change or allosteric state in the β 1 -adrenoceptor molecule. In this context, it is interesting to note recent reports that receptors can have distinct phenotypes even though the origin is the same receptor gene (4,5,24,25). Recently, we have demonstrated that the α 1L -adrenoceptor is derived from the α 1A -adrenoceptor gene but is a distinct phenotype from the classical α 1A -adrenoceptor (25,26).…”