Identification of alpha 1-adrenoceptor subtypes in the dog prostate.

Abstract

The alpha 1-adrenoceptor subtypes of dog prostate were characterized in binding and functional experiments. In saturation experiments, [3H]prazosin bound to alpha 1-adrenoceptors with high affinity. In the displacement experiments, unlabelled prazosin and WB4101 biphasically inhibited the binding of 400 pM [3H]prazosin, suggesting the presence of at least two distinct affinity sites for prazosin or WB4101. The proportion of high-affinity sites was approximately 10%. HV723 also recognized two distinct affinity sites but the proportion of high-affinity sites was approximately 20%. From these results the presence of three distinct alpha 1-adrenoceptor subtypes was suggested: presumably subtypes alpha 1A (high affinity for prazosin and WB4101), alpha 1N (high affinity for only HV723) and alpha 1L (low affinity for the three antagonists) according to the recently proposed alpha 1-adrenoceptor subclassification. The density of subtype alpha 1L was much higher than that of subtypes alpha 1A and alpha 1N subtypes. In the functional experiments, prazosin, WB4101 and HV723 competitively antagonized the contractile response to noradrenaline with low affinities close to those estimated for the alpha 1L subtypes. These results suggest that the contractile response to noradrenaline in the dog prostate is mediated predominantly through alpha 1L subtype alpha-adrenoceptors.