Effects of hydrastine derivatives on dopamine biosynthesis in PC12 cells.

ABSTRACT

The effects of hydrastine derivatives on dopamine biosynthesis in PC12 cells were investigated. Treatments of PC12 cells with (1R,9S)-beta-hydrastine hydrochloride [(+)-beta-hydrastine HCl] and (1R,9S)-beta-hydrastine [(-)-beta-hydrastine] showed 50.6 % and 33.1 % inhibition of dopamine content at a concentration of 10 microM for 48 h. However, (1S,9R)-beta-hydrastine [(+)-beta-hydrastine] and hydrastinine hydrochloride did not reduce dopamine content. The IC(50) values of (1R,9S)-beta-hydrastine hydrochloride and (1R,9S)-beta-hydrastine were 9.3 microM and 20.7 microM , respectively. Next, the intracellular mechanisms of (1R,9S)-beta-hydrastine hydrochloride in PC12 cells were investigated. Dopamine content decreased at 6 h and reached a minimal level at 24 h after the exposure of PC12 cells to 20 microM (1R,9S)-beta-hydrastine hydrochloride. Tyrosine hydroxylase (TH) activity was inhibited at 6 h following the treatment with (1R,9S)-beta-hydrastine hydrochloride, and was maintained at a reduced level for up to 36 h in PC12 cells (17 - 27 % inhibition at 20 microM), whereas TH mRNA level was not found to alter for 24 h. However, the level of intracellular Ca++ concentration decreased by treatment with (1R,9S)-beta-hydrastine hydrochloride at 20 microM by 18.4 % inhibition relative to the control level in PC12 cells. These results suggest that (1R,9S)-beta-hydrastine hydrochloride contributes partially to the decrease in dopamine content by the inhibition of TH activity in PC12 cells.