Amantadine increases aromatic L-amino acid decarboxylase mRNA in PC12 cells.
Amantadine is an antiviral agent that was unexpectedly found to cause symptomatic improvement in patients with Parkinsonism, although its mechanism of action remains to be elucidated. Aromatic L-amino acid decarboxylase (AADC) is a regulated enzyme that catalyzes the decarboxylation of 3,4-dihydroxyphenylalanine (L-Dopa). It may be especially important during L-Dopa therapy in Parkinsonism, during which it may be rate-limiting for the production of dopamine. This study reports the effects of amantadine on the gene expression of AADC in PC12 cells. It shows that amantadine induces AADC gene expression at concentrations of 10 and 100 microM after 24 hr of incubation. The results suggest that the stimulation of AADC mRNA by amantadine may be one of its effects on dopamine metabolism that may have relevance for potentiation of L-Dopa therapy in Parkinsonism.
Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada. lixinm@sask.usask.ca
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D000547:Amantadine / Q000494:pharmacology*; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000096:biosynthesis / Q000235:genetics*; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007700:Kinetics; D016716:PC12 Cells; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects
D012333:RNA, Messenger; D000547:Amantadine; D001142:Aromatic-L-Amino-Acid Decarboxylases