Effects of anonaine on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells.
The effects of anonaine, an aporphine isoquinoline alkaloid, on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Anonaine at concentration ranges of 0.01-0.2 microM showed a significant inhibition of dopamine content at 24 h, with an IC(50) value of 0.05 microM. Anonaine at 0.05 microM inhibited tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) activities to 38.4-40.2% and 78.4-90.2% of control levels at 12-24 h and 3-6 h, respectively. TH activity was more influenced than AADC activity. Anonaine also decreased intracellular cyclic AMP levels, but not intracellular Ca(2+) concentrations. In addition, anonaine (0.05 microM) reduced L-DOPA (50 microM and 100 microM)-induced increases in dopamine content at 24 h. However, anonaine (0.05 microM) did not enhance L-DOPA (50 microM and 100 microM)-induced cell death after 24 h. These results suggest that anonaine inhibits dopamine biosynthesis by mainly reducing TH activity without aggravating L-DOPA-induced cytotoxicity in PC12 cells.
Lee
Jae Joon
JJ
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, 12, Gaeshin-dong, Heungduk-gu, Cheongju 361-763, Korea. jaejlee@hanmail.net
Jin
Chun Mei
CM
Kim
Young Kyoon
YK
Ryu
Shi Yong
SY
Lim
Sung Cil
SC
Lee
Myung Koo
MK
D000818:Animals; D001060:Aporphines / Q000737:chemistry; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004149:Dioxoles / Q000737:chemistry / Q000494:pharmacology*; D004298:Dopamine / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D007980:Levodopa / Q000633:toxicity*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D001060:Aporphines; D004149:Dioxoles; D007546:Isoquinolines; D012333:RNA, Messenger; C098138:anonaine; D007980:Levodopa; D000242:Cyclic AMP; C026980:liriodenine; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D002118:Calcium; D004298:Dopamine