title: Liriodenine inhibits dopamine biosynthesis and L-DOPA-induced dopamine content in PC12 cells.
abstract: 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 microM liriodenine significantly decreased the intracellular dopamine content in a concentration-dependent manner (IC50 value, 8.4 microM). Liriodenine was not cytotoxic toward PC12 cells at concentrations up to 20 microM. Tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) activities were inhibited by 10 microM 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 microM liriodenine. In addition, 10 microM liriodenine reduced L-DOPA (20-100 microM)-induced increases in dopamine content. However, 10 microM liriodenine resulted in a protective effect against L-DOPA (50-100 microM)-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.
authors: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Korea.
authors: Chun Mei
authors: CM
authors: Jin
authors: Jae Joon
authors: JJ
authors: Lee
authors: Yoo Jung
authors: YJ
authors: Yang
authors: Yu Mi
authors: YM
authors: Kim
authors: Young Kyoon
authors: YK
authors: Kim
authors: Shi Yong
authors: SY
authors: Ryu
authors: Myung Koo
authors: MK
authors: Lee
mesh_terms: D000818:Animals; D001060:Aporphines / Q000302:isolation & purification / Q000494:pharmacology*; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D018492:Dopamine Antagonists / Q000302:isolation & purification / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology*; D031566:Magnolia / Q000737:chemistry; D016716:PC12 Cells; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D001060:Aporphines; D018492:Dopamine Antagonists; D007980:Levodopa; D000242:Cyclic AMP; C026980:liriodenine; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D002118:Calcium; D004298:Dopamine