REGULATION OF DOPA DECARBOXYLASE ACTIVITY IN BRAIN OF LIVING RAT

To test the hypothesis that L-DOPA decarboxylase (DDC) is a regulated enzyme in the synthesis of dopamine (DA), we developed a model of the cerebral uptake and metabolism of [H-3]DOPA. The unidirectional blood- brain clearance of [H-3]DOPA (K-1(D)) was 0.049 ml g(-1) min(-1). The relative DDC activity (k(3)(D)) was 0.26 min(-1) in striatum, 0.04 min (-1) in hypothalamus, and 0.02 min(-1) in hippocampus. In striatum, 3, 4-[H-3] dihydroxyphenylacetic acid ([H-3] DOPAC) was formed from [H-3] DA with a rate constant of 0.013 min(-1), [H-3]homovanillic acid ([H-3 ]HVA) was formed from [H-3]DOPAC at a rate constant of 0.020 min(-1), and [H-3]HVA was eliminated from brain at a rate constant of 0.037 min (-1). Together, these rate constants predicted the ratios of endogenou s DOPAC and HVA to DA in rat striatum. Pargyline, an inhibitor of DA c atabolism, substantially reduced the contrast between striatum and cor tex, in comparison with the contrast seen in autoradiograms of control rats. At 30 min and at 4 h after pargyline, k(3)(D) was reduced by 50 % in striatum and olfactory tubercle but was unaffected in hypothalamu s, indicating that DDC activity is reduced in specific brain regions a fter monoamine oxidase inhibition. Thus, DDC activity may be a regulat ed step in the synthesis of DA.