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Molecules 2008, 13(2), 475-487; doi:10.3390/molecules13020475

Effects of Anonaine on Dopamine Biosynthesis and L-DOPA-Induced Cytotoxicity in PC12 Cells

1, 1, 2, 3, 1 and 1,*
1 College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, 12, Gaeshin-dong, Heungduk-gu, Cheongju 361-763, Korea 2 College of Forest Science, Kookmin University, Seoul 136-702, Korea 3 Korea Research Institute of Chemical Technology, Taejeon 305-606, Korea
* Author to whom correspondence should be addressed.
Received: 30 January 2008 / Revised: 22 February 2008 / Accepted: 25 February 2008 / Published: 27 February 2008
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
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The effects of anonaine, an aporphine isoquinoline alkaloid, on dopaminebiosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Anonaineat concentration ranges of 0.01-0.2 μM showed a significant inhibition of dopaminecontent at 24 h, with an IC50 value of 0.05 μM. Anonaine at 0.05 μM inhibited tyrosinehydroxylase (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 wasmore influenced than AADC activity. Anonaine also decreased intracellular cyclic AMPlevels, but not intracellular Ca2+ concentrations. In addition, anonaine (0.05 μM) reducedL-DOPA (50 μM and 100 μM)-induced increases in dopamine content at 24 h. However,anonaine (0.05 μM) did not enhance L-DOPA (50 μM and 100 μM)-induced cell death 476after 24 h. These results suggest that anonaine inhibits dopamine biosynthesis by mainlyreducing TH activity without aggravating L-DOPA-induced cytotoxicity in PC12 cells.
Keywords: Anonaine; Dopamine biosynthesis; L-DOPA-induced cytotoxicity; PC12 cells. Anonaine; Dopamine biosynthesis; L-DOPA-induced cytotoxicity; PC12 cells.
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Lee, J.J.; Jin, C.M.; Kim, Y.K.; Ryu, S.Y.; Lim, S.C.; Lee, M.K. Effects of Anonaine on Dopamine Biosynthesis and L-DOPA-Induced Cytotoxicity in PC12 Cells. Molecules 2008, 13, 475-487.

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