The O-methylated derivative of L-DOPA, 3-O-methyl-L-DOPA, fails to inhibitneuronal and non-neuronal aromatic L-amino acid decarboxylase

The present study examined whether the O-methylated derivative of L-DOPA, 3 -O-methyl-L-DOPA (3-OM-L-DOPA), inhibits neuronal (brain) and non-neuronal (liver and kidney) aromatic L-amino acid decarboxylase (AADC) activity. The incubation of brain, liver and kidney homogenates with 3-OM-L-DOPA (5 mM) did not result in the formation of 3-methoxytyramine, the compound expected to result from the decarboxylation of 3-OM-L-DOPA. Incubation of tissue ho mogenates with L-DOPA resulted in a concentration-dependent formation of do pamine, revealing K-m values (in mM) of similar magnitude for brain (0.8), liver (1.6) and kidney (1.0). Both benserazide and L-5-hydroxytryptophan (L -5-HTP) were found to produce concentration dependent decreases in AADC act ivity with K-i values in the mu M range. By contrast, 3-OM-L-DOPA did not r educe the activity of either neuronal AADC (brain) or non-neuronal AADC (li ver and kidney). The administration of benserazide in vivo (1, 3 and 10 mg/ kg) produced marked reductions in AADC activity in both liver and kidney, b ut had no effect upon brain AADC. The effect of increasing the dose of bens erazide up to 30 mg/kg (p.o.) was an almost complete inhibition (>95% reduc tion) in liver and kidney AADC activity accompanied by a marked decrease (4 9% reduction) in brain AADC activity. By contrast, the administration of 30 mg/kg (p.o.) 3-OM-L-DOPA, which generates levels in brain, liver and kidne y six-fold those in L-DOPA-treated rats, was found to change neither neuron al nor non-neuronal AADC activity. In conclusion, 3-OM-L-DOPA fails to inte ract with neuronal and non-neuronal AADC, either as substrate or inhibitor. (C) 2000 Elsevier Science B.V. All rights reserved.