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 μM showed a significant inhibition of dopamine content at 24 h, with an IC(50) value of 0.05 μM. Anonaine at 0.05 μM 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 μM) reduced l-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 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.