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

Abstract

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 homogenates with l-DOPA resulted in a concentration-dependent formation of dopamine, 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 activity with K i values in the μM range. By contrast, 3-OM- l-DOPA did not reduce the activity of either neuronal AADC (brain) or non-neuronal AADC (liver 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, but had no effect upon brain AADC. The effect of increasing the dose of benserazide up to 30 mg/kg (p.o.) was an almost complete inhibition (>95% reduction) in liver and kidney AADC activity accompanied by a marked decrease (49% 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 kidney six-fold those in l-DOPA-treated rats, was found to change neither neuronal nor non-neuronal AADC activity. In conclusion, 3-OM- l-DOPA fails to interact with neuronal and non-neuronal AADC, either as substrate or inhibitor.