SIGNIFICANCE OF TYROSINE HYDROXYLASE ACTIVATION IN THE REGULATION OF DOPAMINE SYNTHESIS

Abstract

Injections of haloperidol or (+) butaclamol produce a dose-dependent increase in striatal tyrosine hydroxylase (TH) activity as measured in vitro and in the rate of DOPA accumulation in vivo. The relationship between the increase in the rate of DOPA accumulation and the increase in TH activity is linear; the slope of the regression line is dependent on the concentration of the cofactor in the TH assay and in the presence of 0.2 mM 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropterine (DMPH4) is close to unity. In the substantia nigra haloperidol does not influence TH activity but increases DOPAC levels. Similarly, electrical stimulation of the nigrostriatal pathway increases TH activity and DOPAC levels in striatum but in the substantia nigra it affects only DOPAC levels. These results suggest that the change in the kinetic properties of TH is the molecular mechanism regulating dopamine synthesis in axon terminals but not in the cell body-dendritic complex.