Identification of α₁-adrenoceptor subtypes in the dog prostate

Summary

The α₁-adrenoceptor subtypes of dog prostate were characterized in binding and functional experiments. In saturation experiments, [³H]prazosin bound to α₁-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 α₁-adrenoceptor subtypes was suggested: presumably subtypes α_1A (high affinity for prazosin and WB4101), α_1N (high affinity for only HV723) and α_1L (low affinity for the three antagonists) according to the recently proposed α₁-adrenoceptor subclassification. The density of subtype α_1L was much higher than that of subtypes α_1A and α_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 α_1L subtypes. These results suggest that the contractile response to noradrenaline in the dog prostate is mediated predominantly through α_1L subtype α-adrenoceptors.