Inhibitory Effects of Tetrahydropapaveroline on Dopamine Biosynthesis in PC12 Cells

Tetrahydropapaveroline (THP) at 5-15 ${\mu}$M has been found to induce L-DOPA-induced oxidative apoptosis in PC12 cells. In this study, the inhibitory effects of THP on dopamine bios ynthesis in PC12 cells and tyrosine hydroxylase (TH) activity in bovine adrenal were investigated. Treatment of PC12 cells with THP at 2.5-10 ${\mu}$M significantly decreased the intracellular dopamine content in a concentration-dependent manner (18.3% inhibition at 10 ${\mu}$M THP). In these conditions, TH activity was markedly inhibited by the treatment with THP at 2.5-10 ${\mu}$M in PC12 cells (23.4% inhibition at 10 $\mu$ M THP). In addition, THP had an inhibitory effect on bovine adrenal TH activity IC50 value, 153.9${\mu}$M). THP exhibited uncompetitive inhibition on bovine adrenal TH activity with a substrate L-tyrosine with the KI value of 0.30 mM. Treatment with L-DOPA at 20~50 ${\mu}$M increased the intracellular dopamine content in PC12 cells, and the increase in dopamine content by L-DOPA was inhibited in part when THP at non-cytotoxic (5-10 ${\mu}$M) or cytotoxic (15${\mu}$M) concentrations was associated with L-DOPA (20 and 50 ${\mu}$M) for 24 h incubation. These results suggest that THP at 5-10${\mu}$M decreases the basal dopamine content and reduces the increased dopamine content induced by L-DOPA in part by the inhibition of TH activity, and that THP at 15${\mu}$M also decreases dopamine content by oxidative stress in PC12 cells.

Tetrahydropapaveroline의 PC12 세포내 Dopamine 생합성 저해작용