IDENTIFICATION OF ALPHA-1-ADRENOCEPTOR SUBTYPES IN THE DOG PROSTATE

The alpha1-adrenoceptor subtypes of dog prostate were characterized in binding and functional experiments. In saturation experiments, [H-3]p razosin bound to alpha1-adrenoceptors with high affinity. In the displ acement experiments, unlabelled prazosin and WB4101 biphasically inhib ited the binding of 400 pM [H-3]prazosin, suggesting the presence of a t least two distinct affinity sites for prazosin or WB4101. The propor tion of high-affinity sites was approximately 10%. HV723 also recogniz ed two distinct affinity sites but the proportion of high-affinity sit es was approximately 20%. From these results the presence of three dis tinct alpha1-adrenoceptor subtypes was suggested: presumably subtypes alpha1A (high affinity for prazosin and WB4101), alpha1N (high affinit y for only HV723) and alpha1L (low affinity for the three antagonists) according to the recently proposed alpha1-adrenoceptor subclassificat ion. The density of subtype alpha1L was much higher than that of subty pes alpha1A and alpha1N subtypes. In the functional experiments, prazo sin, WB4101 and HV723 competitively antagonized the contractile respon se to noradrenaline with low affinities close to those estimated for t he alpha1L subtypes. These results suggest that the contractile respon se to noradrenaline in the dog prostate is mediated predominantly thro ugh alpha1L subtype alpha-adrenoceptors.