INCREASE IN TYROSINE HYDROXYLASE ACTIVITY AFTER RESERPINE ADMINISTRATION

¹ Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland

After the administration of reserpine, the in vitro tyrosine hydroxylase activity increases in rat, guinea-pig, mouse and rabbit adrenal gland, in rat superior cervical ganglia and in rabbit brainstem. The increase in enzyme activity of rat ganglia and adrenals was dose-dependent up to 5 mg/kg and persisted for at least four days after reserpine was given. Repeated doses of reserpine produced an even greater increase in tyrosine hydroxylase activity. The increase in enzyme activity did not appear to be due to the appearance of an activator or loss of an inhibitor. The K_m for tyrosine and pteridine co-factor with enzyme prepared from reserpine-treated animals was not significantly different from that of control animals; however, a significant increase in V_max for both substrate and co-factor was observed. These results suggest that prolonged periods of drug-induced sympathoadrenal hyperactivity can increase the amount of tyrosine hydroxylase in adrenergic areas of the central and peripheral nervous systems.

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