The O-methylated derivative of L-DOPA, 3-O-methyl-L-DOPA, fails to inhibit neuronal 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 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 microM range. By contrast, 3-OM-L95% 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.
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Institute of Pharmacology and Therapeutics, Faculty of Medicine, 4200, Porto, Portugal. patricio.soares@mail.telepac.pt
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D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000187:drug effects* / Q000378:metabolism*; D001545:Benserazide / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D010300:Parkinson Disease / Q000188:drug therapy; D051381:Rats; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D014443:Tyrosine; D001545:Benserazide; D006916:5-Hydroxytryptophan; D001142:Aromatic-L-Amino-Acid Decarboxylases; C008404:3-methoxytyrosine