The pharmacological profile of cloned and stably expressed α1B-adrenoceptor in CHO cells

Using Chinese hamster ovary (CHO) cells stably expressing the alpha 1B-adrenoceptor (CHO alpha 1B cells) as a model, we investigated whether the transfected cells that express alpha 1B subtype of adrenoceptor can show the pharmacologic characteristics as previously defined in native tissues. Radioligand binding studies with 2-[beta-(4-hydroxy-3-[125I]iodophenyl)ethylamino-methyl]tetralone ([125I]HEAT) in CHO alpha 1B cells showed the similar Ki values of the alpha 1-adrenoceptor selective drugs as previously observed in rat liver and spleen, and that pretreatment with chlorethylclonidine markedly inactivated the binding sites (94.7-98.6%). In CHO alpha 1B cells alpha 1-adrenoceptor agonists caused a dose-dependent increase in transients of cytosolic Ca2+ concentrations ([Ca2+]i), and the potency order of antagonists in inhibiting norepinephrine-induced [Ca2+]i response was similar to that observed in radioligand binding assays. In summary, the present study shows that the ligand binding property, the pharmacological characteristics and the intracellular transduction mechanisms of alpha 1B-adrenoceptors stably expressed in CHO cells appear to be the same as those defined in native tissues. Thus they can be a useful model system for further characterization of the receptor as well as for the development of specific ligands.