Inhibition of Tyrosine Hydroxylase by (1R,9S)-β-Hydrastine Hydrochloride in PC12 Cells

다국어 초록 (Multilingual Abstract)

It is reported that (1R,9S)-b-hydrastine hydrochloride (BHSH) decreased the intracellular dopamine content by inhibiting tyrosine hydroxylase (TH) activity in PC12 cells. In this study, the inhibitory mechanisms on TH activity by BHSH in PC12 cells were investigated. BHSH treatment caused a reduction of TH activity and TH mRNA level in a dose-dependent manner. After the treatment of 20 mM BHSH, TH activity and TH mRNA content were reduced at 15 min, reached the minimal levels at 6-24 h, and then recovered gradually to the control level. BHSH at 10-50 mM caused a decrease in the basal intracellular cyclic AMP levels at 10 min in a concentration-dependent manner. In addition, BHSH at 20-100 mM decreased the basal intracellular Ca2+ concentration ([Ca2+]i) immediately in
a dose-dependent manner. BHSH also inhibited the 56 mM K+ depolarization-induced elevation in [Ca2+]i, and blocked caffeine-activated store-operated Ca2+ entry in PC12 cells. These data suggest that BHSH inhibits TH activity and TH gene expression, in part, through reducing cyclic AMP content and basal [Ca2+]i in PC12 cells.

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