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)-β-hydrastine hydrochloride [(+)-β-hydrastine HCl] and (1R,9S)-β-hydrastine [(-)-β-hydrastine] showed 50.6 % and 33.1 % inhibition of dopamine content at a concentration of 10 μM for 48 h. However, (1S,9R)-β-hydrastine [(+)-β-hydrastine] and hydrastinine hydrochloride did not reduce dopamine content. The IC₅₀ values of (1R,9S)-β-hydrastine hydrochloride and (1R,9S)-β-hydrastine were 9.3 μM and 20.7 μM, respectively. Next, the intracellular mechanisms of (1R,9S)-β-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 μM (1R,9S)-β-hydrastine hydrochloride. Tyrosine hydroxylase (TH) activity was inhibited at 6 h following the treatment with (1R,9S)-β-hydrastine hydrochloride, and was maintained at a reduced level for up to 36 h in PC12 cells (17 - 27 % inhibition at 20 μM), 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)-β-hydrastine hydrochloride at 20 μM by 18.4 % inhibition relative to the control level in PC12 cells. These results suggest that (1R,9S)-β-hydrastine hydrochloride contributes partially to the decrease in dopamine content by the inhibition of TH activity in PC12 cells.

(1R,9S)-β-Hydrastine - (1S,9R)-β-hydrastine - Corydalis stricta - Papaveraceae - Hydrastis canadensis - Ranunculaceae - Berberis laurina - Berberidaceae - dopamine content - tyrosine hydroxylase - TH mRNA - intracellular Ca⁺⁺ concentration - PC12 cells

References

• 1 Tang W, Eisenbrand G. Corydalis turtschaninovii Bess f. yanhusuo . Y.H. Chou et C.C. Hsu In: Chinese Drugs of Plant Origin. Springer Verlag Heidelberg; 1992: 377-93
• 2 Stanek J, Manske R HF. Phthalide Isoquinoline Alkaloids. In: The Alkaloids, Chemistry and Physiology. Manske RHF, Holmes HL, editors Academic Press Inc New York; 1968: 167-98
• 3 Huang J H, Johnston G AR. (+)-Hydrastine, a Potent Competitive Antagonist at Mammalian GABAA Receptors.  Br. J. Pharmacol.. 1990;  99 727-30
• 4 Tischler A S, Perlman R L, Morse G M, Sheard B E. Glucocorticoids increase catecholamine synthesis and storage in PC12 pheochromocytoma cell cultures.  J. Neurochem.. 1983;  40 364-70
• 5 Byrd J C, Hadjiconstantinou M, Cavalla D. Epinephrine synthesis in the PC12 pheochromocytoma cell line.  Eur. J. Pharmacol.. 1986;  127 139-42
• 6 Gebreyesus K, Kilbourne E J, Sabban E L. Bradykinin elevates tyrosine hydroxylase and dopamine β-hydroxylase mRNA in PC12 cells.  Brain Res.. 1993;  608 345-8
• 7 Shin J S, Kim E I, Kai M, Lee M K. Inhibition of dopamine biosynthesis by protoberberine alkaloids in PC12 cells.  Neurochem. Res.. 2000;  25 363-8
• 8 Shin J S, Kim K T, Lee M K. Inhibitory effects of bulbocapnine on dopamine biosynthesis in PC12 cells.  Neurosci. Lett.. 1998;  244 161-4
• 9 Shin J S, Yun-Choi H S, Kim E I, Lee M K. Inhibitory effects of higenamine on dopamine content in PC12 cells.  Planta Med.. 1999;  65 452-5
• 10 Lee M K, Zhang Y H. Inhibition of tyrosine hydroxylase by berberine.  Med. Sci. Res.. 1996;  24 561-2
• 11 Lee M K, Zhang Y H, Shin J S, Lee S S. Inhibition of tyrosine hydroxylase by hydrastine.  Med. Sci. Res.. 1997;  25 619-20
• 12 Mitsui A, Nohta H, Ohkura Y. High-performance liquid chromatography of plasma catecholamines using 1,2-diphenylethylenediamine as precolumn fluorescence derivatization reagent.  J. Chromatogr.. 1985;  344 61-70
• 13 Nagatsu T, Oka K, Kato K. Highly sensitive assay for tyrosine hydroxylase activity by high-performance liquid chromatography.  J. Chromatogr.. 1979;  163 247-52
• 14 Lee M K, Nohta H, Ohkura Y. Occurrence of aromatic L-amino acid decarboxylase in human plasma and its assay by high-performance liquid chromatography with fluorescence detection.  J. Chromatogr.. 1986;  378 329-36
• 15 Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.  Anal. Biochem.. 1987;  162 156-9
• 16 Kim K S, Park D H, Wessel T C, Song B, Wagner J A, Joh T H. A dual role for the cAMP-dependent protein kinase in tyrosine hydroxylase gene expression. Proc. Natl. Acad. Sci.  USA. 1993;  90 3471-5
• 17 Grynkiewicz G, Poeni M, Tsien R Y. A new generation of Ca⁺⁺ indicators with greatly improved fluorescence properties.  J. Biol. Chem.. 1985;  260 3440-50
• 18 Lowry O H, Rosebrough N J, Farr A L, Randall R J. Protein measurement with the folin phenol reagent.  J. Biol. Chem.. 1951;  193 265-75
• 19 Dunkley P R, Cote A, Harrison S M, Herd L, Hall A, Powis D A. Tyrosine hydroxylase phosphorylation in bovine adrenal chromaffin cells.  Biochem. Pharmacol.. 1996;  51 239-45
• 20 Kim K S, Lee M K, Carroll J, Joh T H. Both basal and inducible transcription of the tyrosine hydroxylase gene are dependent upon a cAMP response element.  J. Biol. Chem.. 1993;  268 15 689-95