Partial destruction of noradrenergic terminals is followed by increased tyrosine hydroxylase activity in residual terminals

Abstract

Intraventricular administration of 6-hydroxydopamine produced a relatively small decline in tyrosine hydroxylase (TH) activity in rat hippocampus despite the widespread degeneration of central noradrenergic nerve terminals. This increase in the ratio of TH activity to norepinephrine content appeared to result from two temporally distinct processes. At first, within 36 hours after the lesion, the apparent Vmax of TH decreased in parallel to the loss of norepinephrine but there was a marked increase in the affinity of the enzyme for cofactor, resembling the effects of in vitro phosphorylation. Subsequently, this activation of the enzyme declined but the apparent V_max of TH gradually increased in a manner suggesting an increase in the amount of TH per residual terminal. These short and long term alterations in TH activity after 6-hydroxydopamine treatment may represent adaptive responses to the lesion.