Tyrosine hydroxylase activity in the sympathoadrenal system under basal and stressful conditions: effect of 6-hydroxydopamine.

Subtotal destruction of central noradrenergic neurons with the neurotoxin, 6-hydroxydopamine, is known to increase tyrosine hydroxylase (TH) activity within surviving nerve terminals. The present report demonstrates a similar, dose-related elevation of TH activity in the adrenal medulla and sympathetic nerves after systemic 6-hydroxydopamine treatment. Two temporally distinct processes were observed in the sympathetic nerves: a rapid activation of TH, present during the first few days after the lesion, and a more gradual increase in maximal TH activity, most probably due to enzyme induction. In this regard, the stimulatory effect on catecholamine biosynthesis of cyclic AMP-dependent phosphorylation was attenuated substantially within cardiac sympathetic nerves 3 days after the lesion, but by 3 weeks the efficacy of cyclic AMP-dependent phosphorylation was restored completely. Similarly, the normal activation of cardiac TH activity elicited by insulin-induced hypoglycemia and cold stress was absent soon after 6-hydroxydopamine treatment, but returned 3 weeks later. These latter findings suggest that the adaptations within the sympathoadrenal system after subtotal sympathectomy can preclude further adaptations to stress.