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KMID : 0620720040100030114
Natural Product Sciences
2004 Volume.10 No. 3 p.114 ~ p.118
Inhibition of Tyrosine Hydroxylase by (1R,9S)-¥â-Hydrastine Hydrochloride in PC12 cells
Yin Shou-Yu

Kim Yu-Mi
Lee Jae-Joon
Jin Chun-Mei
Yang Yoo-Jung
Lim Kyo-Whan
Kang Min-Hee
Lee Myung-Koo
Abstract
It is reported that (1R,9S)-¥â-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 ¥ìM 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 ¥ìM caused a decrease in the basal intracellular cyclic AMP levels at 10 min in a concentration-dependent manner. In addition, BHSH a 20-100 ¥ìM decreased the basal intracellular Ca©÷+ concentration ([Ca©÷+]i) immediately in a dose-dependent manner. BHSH also inhibited the 56 mM K+ depolarization-induced elevation in [Ca©÷+]i, and blocked caffeine-activated store-operated Ca©÷+ 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 [Ca©÷+]i in PC12 cells.
KEYWORD
(1R, 9S)-¥â-Hydrastine hydrochloride, Tyrosine hydroxylase, Cyclic AMP, [Ca©÷+]i, PC12 cells
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