Effect of triamterene on tyrosine hydroxylase activity

Summary

Triamterene, which is structurally similar to the natural cofactor of tyrosine hydroxylase, (6R)-l-erythro-5,6,7,8-tetrahydrobiopterin, inhibited tyrosine hydroxylase in rat adrenal gland homogenates and was found to be a competitive inhibitor of the synthetic cofactor 6,7-dimethyl-5,6,7,8-tetrahydrobiopterin. When triamterene (30 mg/kg i.p.) was administered to rats, a significant decrease in the adrenal, whole brain and kidney enzyme activities was observed after 90 min; if the drug was given orally, the diuretic affected only adrenal tyrosine hydroxylase. In both cases the drug decreased potassium excretion to 1/5 of control values and increased the excretion of sodium. Catecholamine levels in atria, kidneys, adrenal glands and whole brain were not affected in acute experiments. Chronic treatment (triamterene 30 mg/kg p.o. twice daily during 4 days) inhibited tyrosine hydroxylase and decreased catecholamine levels in the kidneys. Low potassium excretion was observed throughout the 4 days of treatment. In these chronic experiments the inhibition of the adrenal enzyme seen in acute treatments was not observed. This recovery cannot be explained by increase in the adrenal biopterin levels. It could be mediated by an induction of the adrenal tyrosine hydroxylase.