Regulation of synaptosomal tyrosine hydroxylation in different brain regions with noradrenergic innervation

Tyrosine hydroxylation rate was measured by a modified tritium release assay at the physiological pH of 7.4 in synaptosomes prepared from cerebellum, hippocampus and hypothalamus. Incubation in the presence of 2 mM 8 bromo cAMP increased tyrosine hydroxylation in all three regions. An almost identical activation was seen after membrane depolarization by 50 mM K⁺. Removal of Ca²⁺ from the incubation medium had no significant effect on the activation produced by either agent, however it did significantly increase the control tyrosine hydroxylation rate in the hypothalamus. The combined effect of 8 Br cAMP and high K⁺ was found to be additive in the cerebellum and hippocampus but not in the hypothalamus. A reduction in tyrosine hydroxylation was observed if incubation was carried out in the presence of 1 μM noradrenaline; the degree of inhibition was similar in the three regions. 2 mM 8 Br. cAMP added to the noradrenaline restored tyrosine hydroxylation to control levels in synaptosomes from the hypothalamus, but not the hippocampus and cerebellum. Tyrosine hydroxylase in the hypothalamus is associated with dopaminergic nerve terminals as well as noradrenergic nerve terminals derived from more than one cell group, the hippocampus and cerebellum however both receive their noradrenergic input entirely from the locus coeruleus. Differences between synaptosomes from the three brain regions may therefore reflect differences in the nature of the enzyme as well as local regulatory mechanisms.