Effects of hydrastine derivatives on dopamine biosynthesis in PC12 cells.
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.
Kim
S H
SH
College of Pharmacy, Chungbuk National University, Kaeshin-Dong, Heungduk-Ku, Cheongju 361-763, Republic of Korea.
Shin
J S
JS
Lee
J J
JJ
Yin
S Y
SY
Kai
M
M
Lee
M K
MK
D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D044182:Benzylisoquinolines; D028142:Berberis / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D004298:Dopamine / Q000032:analysis / Q000096:biosynthesis*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D016716:PC12 Cells; D028101:Papaveraceae / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D012333:RNA, Messenger; D029626:Ranunculaceae / Q000737:chemistry; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000470:Alkaloids; D044182:Benzylisoquinolines; D012333:RNA, Messenger; C013024:hydrastine; D006899:Mixed Function Oxygenases; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D002118:Calcium; D004298:Dopamine