Catalponol enhances dopamine biosynthesis and protects against L-DOPA-induced cytotoxicity in PC12 cells

The effects of catalponol ( 1) on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Catalponol at concentration ranges of 1-5 mu M increased the intracellular levels of dopamine at 12-48 h. Catalponol at concentrations of up to 10 mu M did not alter cell viability. Tyrosine hydroxylase (TH) activity was enhanced by 1 at 3 mu M in a time-dependent manner, but aromatic L-amino acid decarboxylase activity was not. Catalponol also increased the intracellular levels of cyclic AMP and TH phosphorylation. In addition, catalponol at 3 mu M associated with L-DOPA (20-50 mu M) further enhanced the increases in dopamine levels induced by L-DOPA (50-100 mu M) at 24 h. Catalponol at 2-5 mu M inhibited L-DOPA (100-200 mu M)-induced cytotoxicity at 48 h. These results suggest that 1 enhanced dopamine biosynthesis by inducing TH activity and protected against L-DOPA-induced cytotoxicity in PC12 cells, which was mediated by the increased levels of cyclic AMP.