Inhibition of Dopamine-β-Hydroxylase by Hydralazine 1

Abstract

Summary

The effect of the antihypertensive drug, hydralazine (l-hydrazinophthalazine) on the partially purified dopamine-β-hydroxylase from bovine adrenal gland was investigated. The enzyme preparation so prepared was shown to be activated by the appropriate concentration of Cu²⁺ known to inactivate endogenous inhibitors. When the drug was added to this enzyme preparation along with the appropriate components, the inhibition of the hydroxylase enzyme activity could be demonstrated. The inhibition was shown to be noncompetitive, suggesting that the drug did not interfere with the substrate-binding site of the enzyme. The double reciprocal plot of the initial velocity against enzyme concentration shared a common intercept on the abcissa, indicating that DBH activity was inhibited by the drug through a mechanism other than competition for an essential constituent directly involved in the optimum activity of the enzyme. The drug-induced inhibition of the enzyme activity was reversed by adding various concentrations of Cu²⁺ to the system. These data suggest that the drug inhibits DBH activity by chelating Cu²⁺ which is essential for the inactivation of the endogenous inhibitors present in the enzyme preparation used in these experiments.