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Titolo:
The O-methylated derivative of L-DOPA, 3-O-methyl-L-DOPA, fails to inhibitneuronal and non-neuronal aromatic L-amino acid decarboxylase
Autore:
Soares-Da-Silva, P; Parada, A; Serrao, P;
Indirizzi:
Fac Med Porto, Inst Pharmacol & Therapeut, P-4200 Oporto, Portugal Fac MedPorto Oporto Portugal P-4200 Therapeut, P-4200 Oporto, Portugal BIAL, Dept Res & Dev, P-4785 S Mamede Do Coronado, Portugal BIAL S MamedeDo Coronado Portugal P-4785 S Mamede Do Coronado, Portugal
Titolo Testata:
BRAIN RESEARCH
fascicolo: 1-2, volume: 863, anno: 2000,
pagine: 293 - 297
SICI:
0006-8993(20000428)863:1-2<293:TODOL3>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
PARKINSONS-DISEASE; RAT; BRAIN; 3-O-METHYLDOPA; METABOLISM; TRANSPORT; LEVODOPA;
Keywords:
L-DOPA; 3-O-methyl-L-DOPA; aromatic L-amino acid decarboxylase; brain; liver; kidney;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
20
Recensione:
Indirizzi per estratti:
Indirizzo: Soares-Da-Silva, P Fac Med Porto, Inst Pharmacol & Therapeut, P-4200 Oporto, Portugal Fac Med Porto Oporto Portugal P-4200 Oporto, Portugal
Citazione:
P. Soares-Da-Silva et al., "The O-methylated derivative of L-DOPA, 3-O-methyl-L-DOPA, fails to inhibitneuronal and non-neuronal aromatic L-amino acid decarboxylase", BRAIN RES, 863(1-2), 2000, pp. 293-297

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 mu M 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. (C) 2000 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/07/20 alle ore 22:48:14