α_1B-Adrenoceptor-mediated stimulation of Ca²⁺ mobilization and cAMP accumulation in isolated rat hepatocytes

Noradrenaline stimulates not only Ca²⁺ mobilization but also cAMP formation through activation of α₁-adrenoceptors in hepatocytes from mature male rats. We examined which subtype(s) of α₁-adrenoceptor mediate these signal transduction mechanisms. Treatment of hepatocytes with chloroethylclonidine produced a dose-dependent inhibition of noradrenaline-induced Ca²⁺ mobilization, involving both transient and sustained components. Chloroethylclonidine also blocked noradrenaline-induced cAMP accumulation. It was observed that prazosin was much more potent than WB4101 (2-(2,6-dimethoxy-phenoxyethyl)aminomethyl-1,4-benzodioxane) in antagonizing noradrenaline-induced Ca²⁺ mobilization. The same potency order was found in cAMP formation studies. Pretreatment of rats with pertussis toxin did not affect α₁-adrenergic responsiveness. Incubations of hepatocytes with tumor-promoting phorbol esters eliminated both Ca²⁺ mobilization and cAMP accumulation caused by noradrenaline. Our data suggest that in hepatocytes from mature male rats, single α_1B-adrenoceptors are linked to cAMP formation as well as Ca²⁺ mobilization.