Binding and functional characterization of α1-adrenoceptor subtypes in the rat prostate

Abstract The α 1 -adrenoceptor subtypes of rat prostate were characterized in binding and functional experiments. In binding experiments, [ 3 H ]tamsulosin bound to a single class of binding sites with an affinity (p K D ) of 10.79±0.04 and B max of 87±2 fmol mg −1 protein. This binding was inhibited by prazosin, 2-(2,6-dimethoxy-phenoxyethyl)-aminomethyl-1,4-benzodioxane hydrochloride (WB4101), 5-methylurapidil, α-ethyl-3,4,5,-trimethoxy-α-(3-((2-(2-methoxyphenoxy)ethyl)-amino)-propyl)benzeneacetonitrile fumarate (HV723) and oxymetazoline with high efficacy, resulting in a good correlation with the binding characteristics of cloned α 1a but not α 1b and α 1d -adrenoceptor subtypes. In functional studies, noradrenaline and oxymetazoline produced concentration-dependent contractions. These contractions were antagonized by tamsulosin, prazosin, WB4101 and 5-methylurapidil with an efficacy lower than that exhibited by these agents for inhibition of [ 3 H ]tamsulosin binding. The relationship between receptor occupancy and contractile amplitude revealed the presence of receptor reserve for noradrenaline, but the contraction induced by oxymetazoline was not in parallel with receptor occupation and developed after predicted receptor saturation. From these results, it is suggested that α 1A -adrenoceptors are the dominant subtype in the rat prostate which can be detected with [ 3 H ]tamsulosin, but that the functional subtype mediating adrenergic contractions has the characteristics of the α 1L -adrenoceptor subtype, having a lower affinity for prazosin and some other drugs than the α 1A -adrenoceptor subtype.