The antagonistic effect of separate and consecutive chronic treatment with imipramine and ECS on the inhibition of alpha 1-adrenoceptor activity by protein kinase C.

We tested how chronic antidepressant treatments (chronic imipramine, chronic electroconvulsive shock (ECS) and chronic ECS given after chronic imipramine) affect the feedback inhibition of alpha 1-adrenoceptor activity (measured with inositol phosphate (IP) accumulation after stimulation with noradrenaline). The inhibitory effect of a 12-O-tetradecanoylphorbol 13-acetate (TPA) on IP response was found to be due to protein kinase C (PKC) activation, as it was abolished by specific protein kinase inhibitors, staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). Chronic ECS completely abolished the inhibition by TPA of inositol phosphate response to noradrenaline, while chronic imipramine reversed the feedback and led to potentiation of responses by TPA to intermediate concentrations of noradrenaline. Subsequent chronic ECS abolished the imipramine-induced reversal of TPA inhibition and lead to the changes similar as observed after ECS alone. The present results may suggest why in some cases, in which imipramine therapy is ineffective, subsequent ECS may be clinically beneficial.