Characterization of α-adrenoceptors in rat and guinea pig tissues using radiolabeled agonists and antagonists

Tritium-labeled preparations of the selective α₂-adrenoceptor agonist, clonidine, and the selective α₁-adrenoceptor antagonists, prazosin and WB4101, were examined for their suitability as ligands for receptor assay. In the rat brain, ³H-clonidine bound specifically with high affinity to membrane sites, and drug displacement studies indicated that these were α₂-adrenoceptors. The structural requirements for this receptor were defined by examining a range of clonidine analogues. ³H-Clonidine binding to peripheral tissues of the rat was very low, although peripheral tissues from guinea pig exhibited higher binding. Specific ³H-clonidine binding was not reduced after chemical sympathectomy, suggesting that the binding site, although having characteristics of an α₂-adrenoceptor, was not located presynaptically. Studies with ³H-WB 4101 in rat cerebral cortex indicated that this ligand bound to an α₁-adrenoceptor which was independent of the ³H-clonidine binding site. ³H-Prazosin was a ligand for α₁-adrenoceptors in guinea pig brain and also in membranes from seminal vesicle. However, in the latter tissue, characterization of the binding site was hampered by a high degree of nonspecific binding (50% of total binding).