Characterization of alpha-adrenoceptors in rat and guinea pig tissues using radiolabeled agonists and antagonists.
Tritium-labeled preparations of the selective alpha 2-adrenoceptor agonist, clonidine, and the selective alpha 1-adrenoceptor antagonists, prazosin and WB 4101, 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 alpha 2-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-clinidine binding was not reduced after chemical sympathectomy, suggesting that the binding site, although having characteristics of an alpha 2-adrenoceptor, was not located presynaptically. Studies with 3H-WB 4101 in rat cerebral cortex indicated that this ligand bound to an alpha 1-adrenoceptor which was independent of the 3H-clonidine-binding site. 3H-Prazosin was a ligand for alpha 1-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).
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D011224:Prazosin / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha
D004146:Dioxanes; D004147:Dioxins; D011799:Quinazolines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine; D011224:Prazosin