Liriodenine inhibits dopamine biosynthesis and L-DOPA-induced dopamine content in PC12 cells.
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.
Jin
Chun Mei
CM
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Korea.
Lee
Jae Joon
JJ
Yang
Yoo Jung
YJ
Kim
Yu Mi
YM
Kim
Young Kyoon
YK
Ryu
Shi Yong
SY
Lee
Myung Koo
MK
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
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