Reserpine and the monoaminergic regulation of adrenal dopamine beta-hydroxylase activity

The systemic administration of reserpine to rats increases adrenal dopamine beta-hydroxylase activity, but is without significant effect on the Km(tyramine). This induction is partially blocked by hemisplanchnicotomy and by impairment of translation. The combined administration of (a) alpha-methyl-p-tyrosine and p-chlorophenylalanine; (b) 6-hydroxydopamine and p-chlorophenylalanine; or (c) alpha-methyl-p-tyrosine and 5,7-dihydroxytryptamine increases adrenal dopamine beta-hydroxylase activity. These results suggest that the simultaneous depletion of central serotonin and catecholamines, as achieved by reserpine alone or by conjoint action of two specific drugs, is necessary for the induction. p-Chlorophenylalanine (intraperitoneal) or 5,7-dihydroxytryptamine (intracerebroventricular or injected into the medial raphe nucleus) increases the effect of reserpine, but the use of a catecholamine-depleting agent with reserpine does not alter the increase of adrenal dopamine beta-hydroxylase obtained with reserpine alone. The potentiation by 5,7-dihydroxytryptamine is abolished by hemisplanchnicotomy, a result that demonstrates neural mediation of its effect. Although intravenous administration of 6-hydroxydopamine alone increases the activity of adrenal dopamine beta-hydroxylase, the combination of this treatment with p-chlorophenylalanine does not elevate it further, as occurs with intracerebroventricular injections; this suggests a specific role of central catecholamine depletion. The serotonin agonists 5-hydroxytryptophan, fenfluramine and 5-methoxy-N,N-dimethyltryptamine abolish the inducing effect of reserpine. This work sheds light on the action of reserpine as inducer and provides evidence for the role of monoaminergic pathways, with net inhibitory effects, that are involved in the regulation of the activity of an adrenal enzyme.