INVESTIGATION OF ALPHA(1)-ADRENOCEPTOR SUBTYPES IN CANINE AORTA, USING ALKYLATING-AGENTS

The ability of putative selective irreversible ligands SZL-49 (1-(4-amino-6,7-dimethyoxy-2,5-diene-2-carbonyl) and CEC (chlorethylclonidine), for alpha1A and alpha1B adrenoceptor subtypes, respectively, to affect alpha1-adrenoceptors of canine aorta microsomal membranes was investigated. These membranes contain an apparently homogeneous population of [H-3]prazosin binding sites. SZL-49, like phenoxybenzamine, abolished all binding of [H-3]prazosin. CEC abolished 75% of the prazosin binding sites under the most stringent conditions we applied. However, the remaining 25% of binding sites was identical in affinity for prazosin with control membranes, and competition studies of other subtype-selective ligands revealed unchanged ability to compete against CEC-sensitive and -insensitive sites. We concluded that SZL-49 and CEC are not alpha1A-and alpha1B-adrenoceptor selective under in vitro conditions. Our data led to the hypothesis that canine aortic membranes contain exclusively alpha1B-adrenoceptors but that current tools for identifying alpha1-adrenoceptor subtypes proved inadequate in vitro in this study.