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KMID : 0043320070300080984
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Archives of Pharmacal Research
2007 Volume.30 No. 8 p.984 ~ p.990
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Liriodenine Inhibits Dopamine Biosynthesis and L-DOPA-Induced Dopamine Content in PC12 Cells
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Jin Chun Mei
Lee Jae-Joon
Yang Yoo-Jung
Kim Yu-Mi
Kim Young-Kyoon
Ryu Shi-Young
Lee Myung-Koo
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Abstract
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The inhibitory effects of liriodenine, an aporphine isoquinoline alkaloid, on dopamine biosynthesis and L-DOPA-induced dopamine content increases in PC12 cells were investigated. Treatment of PC12 cells with 5-10 μM liriodenine significantly decreased the intracellular dopamine content in a concentration-dependent manner (IC50 value, 8.4 μM). Liriodenine was not cytotoxic toward PC12 cells at concentrations up to 20 μM. Tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) activities were inhibited by 10 μM liriodenine to 20-70% and 10-14% of control levels at 3-12 h, respectively; TH activity was more influenced than AADC activity. The levels of TH mRNA, intracellular cyclic AMP and basal Ca2+ concentration were also decreased by 10 μM liriodenine. In addition, 10 μM liriodenine reduced L-DOPA (20-100 μM)-induced increases in dopamine content. However, 10 μM liriodenine resulted in a protective effect against L-DOPA (50-100 μM)-induced cytotoxicity. These results suggest that liriodenine regulates dopamine biosynthesis by partially reducing TH activity and TH gene expression and has protective effects against L-DOPA-induced cytotoxicity in PC12 cells.
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KEYWORD
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Liriodenine, L-DOPA, Tyrosine hydroxylase, Aromatic L-amino acid decarboxylase, TH mRNA, Cyclic-AMP, Intracellular Ca2+ concentration, PC12 cells
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