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).
|Issue number||6 II|
|Publication status||Published - 1 Dec 1980|