INVITRO EFFECTS OF PH AND PHOSPHORYLATION ON NEOSTRIATAL TYROSINE-HYDROXYLASE FROM CONTROL AND HALOPERIDOL-TREATED RATS

Acute administration of the antipsychotic drug haloperidol to rats causes a marked decrease in the Km of neostriatal tyrosine hydroxylase [TH] for the pteridine cofactor, 6MPH4 [2-amino-5-hydroxy-6-methyltetrahydropterin], with no change in Vmax. The effect is dependent on the pH of the assay mixture. It occurs at pH 6.5 but not at pH 6.0, the pH optimum for TH. With phosphorylating conditions at pH 6.5, the haloperidol-induced activation is no longer seen and the TH kinetics are the same as those from control rats. At pH values of 6.0, 6.3 and 6.5, a significant decrease in Vmax occurs, with increasing pH, while no significant change in Km for the cofactor is seen for TH from control rats. When phosphorylating conditions are empolyed a marked increase in Km for the cofactor is seen while only a slight decrease in Vmax is seen, with increasing pH, for the control enzyme at the 3 pH values tested.