Abstract
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 IC50 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 Ca2+ 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.
Highlights
Anonaine (A, Figure 1) is an aporphine isoquinoline alkaloid isolated from the plant species Magnolia ovobata Thun. (Magnoliaceae)
These results suggest that anonaine inhibits dopamine biosynthesis by mainly reducing tyrosine hydroxylase (TH) activity without aggravating L-DOPA-induced cytotoxicity in PC12 cells
The dopamine content in the medium, which was secreted from intracellular dopamine stores in PC12 cells, was increased to 472% compared to control levels at 30 min by treatment of 0.05 μM anonaine (Figure 2B)
Summary
Anonaine (A, Figure 1) is an aporphine isoquinoline alkaloid isolated from the plant species Magnolia ovobata Thun. (Magnoliaceae). These results suggest that anonaine inhibits dopamine biosynthesis by mainly reducing TH activity without aggravating L-DOPA-induced cytotoxicity in PC12 cells. Aporphine alkaloids such as bulbocapnine and liriodenine (B, Figure 1) showed inhibitory effects on dopamine biosynthesis in PC12 cells [10,11]. The inhibitory effects of anonaine on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were examined.
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