Effects of ginsenosides on GABAA receptor channels expressed in xenopus oocytes
Tóm tắt
Ginsenosides, major active ingredients ofPanax ginseng, are known to regulate excitatory ligand-gated ion channel activity such as nicotinic acetylcholine and NMDA receptor channel activity. However, it is not known whether ginsenosides affect inhibitory ligand-gated ion channel activity. We investigated the effect of ginsenosides on human recombinant GABAA receptor (α1β1γ2S) channel activity expressed inXenopus oocytes using a two-electrode voltage-clamp technique. Among the eight individual ginsenosides examined, namely, Rb1, Rb2, Rc, Rd, Re, Rf, Rg1 and Rg2, we found that Rc most potently enhanced the GABA-induced inward peak current (l
GABA). Ginsenoside Rc alone induced an inward membrane current in certain batches of oocytes expressing the GABAA receptor. The effect of ginsenoside Rc onI
GABA was both dose-dependent and reversible. The half-stimulatory concentration (EC50) of ginsenoside Rc was 53.2 ± 12.3 μM. Both bicuculline, a GABAA receptor antagonist, and picrotoxin, a GABAA channel blocker, blocked the stimulatory effect of ginsenoside Rc onI
GABA. Niflumic acid (NFA) and 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS), both Cl− channel blockers, attenuated the effect of ginsenoside Rc onI
GABA. This study suggests that ginsenosides regulated GABAA receptor expressed inXenopus oocytes and implies that this regulation might be one of the pharmacological actions ofPanax ginseng.
Tài liệu tham khảo
Abe, K., Cho, S. I., Kitagawa, I., Nishiyama, N., and Saito, H. Differential effects of ginsenoside Rb1 and malonylginsenoside Rb2 on long-term potentiation in the dentate gyrus of rat.Brain Res., 649, 7–11 (1994).
Attele, A. S., Wu, J. A., and Yuan, C. S. Ginseng pharmacology: Multiple constituents and multiple actions.Biochem. Pharmacol., 58, 1685–1693 (1999).
Bloom, F., Iversen, L. L., Localizing [3H]GABA in the nerve terminals of rat cerebral cortex by electron microscopic autoradiography.Nature, 229, 628–630 (1971).
Choi, S., Kim, H. J., Ko, Y. S., Jeong, S. W., Kim, Y. I., Simonds, W. F., Oh, J. W., Nah, S.Y. Gαq/11 coupled to mammalian phospholipase C β3-like enzyme mediates the ginsenoside effect on Ca2+-activated Cl− current in theXenopus oocyte.J BioI. Chem., 276, 48797–802 (2001).
Choi, S., Jung, S. Y., Lee, J. H., Sala, F., Criado, M., Mulet, J., Valor, L. M., Sala, S., Engel, A. G., and Nah, S. Y. Effects of ginsenosides, active components of ginseng, on nicotinic acetylcholine receptors expressed inXenopus oocytes.Eur. J. Pharmacal., 442, 37–45 (2002).
Dascal, N. The use ofXenopus oocytes for the study of ion channels.CRC Crit. Rev. Biochem., 22, 317–387 (1987).
Frings, S., Reuter, D., and Kleene, S. J. Neuronal Ca2+-activated Cl− channels homing in on an elusive channel species.Prog. Neurobiol., 60, 247–289 (2000).
Hill-Venning, C., Belelli, D., Peters, J. A., and Lambert, J. J. Subunit dependent interaction of the general anaesthetic etomidate with the γ-aminobutyric acid typeA receptor.Br. J. Pharmacal., 120, 749–756 (1997).
Kim, H. S., Hwang, S. L., Nah, S. Y., and Oh, S. Changes of [3H]MK-801, [3H]muscimol and [3H]flunitrazepam binding in rat brain by the prolonged ventricular infusion of ginsenoside Rc and Rg1.Pharmacal. Res., 43, 473–9 (2001).
Kim, S., Ahn, K., Oh, T H., Nah, S. Y., and Rhim, H. Inhibitory effect of ginsenosides on NMDA receptor-mediated signals in rat hippocampal neurons.Biochem. Biophysical Res. Comm., 296, 247–254 (2002).
Kim, Y. C., Kim, S. R., Markelonis, G. J. and Oh, T. H. Ginsenosides Rb1 and Rg3 protect cultured rat cortical cells from glutamate-induced neurodegeneration.J. Neurosci. Res., 53, 426–432 (1998).
Kimura, T., Saunders, P. A., Kim, H. S., Rheu, H. M., Oh, K. W., and Ho, I. K., Interactions of ginsenosides with ligandbindings of GABAA and GABAB receptors.Gen. Pharmacal., 25, 193–9 (1994).
Krishek, B. J., Moss, S. J., and Smart, T. G., A functional comparison of the antagonists bicuculline and pocrotoxin at recombinant GABAA receptors.J. Neurochem., 36, 1289–1298 (1996).
Kudo, K., Tachikawa, E., Kashimoto, T., and Takahashi, E. Properties of ginseng saponinin hibition of catecholamine secretion in bovine chromaffin cells.Eur. J. Pharmacal., 341, 139–144 (1998).
Macdonald, R. L., and Olsen, R. W., GABAA receptor channels.Ann. Rev. Neurosci., 17, 569–602 (1994).
McCabe, R. T., and Wamsley, J. K., Autoradiographic localization of subcomponents of the macromolecular GABAA receptor complex.Life Sci., 39, 1937–45 (1986).
Ortells, M. O. and Lunt, G. G. Evolutionary history of the ligandgated ion channel superfamily of receptors.Trends Neurosci., 18, 121–127 (1995).
Sala, F., Mulet, J., Choi, S., Jung, S. Y., Nah, S. Y., Rhim, H., Valor, L. M., Criado, M., and Sala, S. Effects of ginsenoside Rg2 on human neuronal nicotinic acetylcholine receptors.J. Pharmacal. Exp. Ther., 301, 1052–1059 (2002).
Seong, Y. H., Shin, C. H., Kim, H. S. and Baba A. Inhibitory effect of ginseng total saponins on glutamate-induced swelling of cultured astrocytes.Biol. Pharm. Bull., 18, 1776–1778 (1995).
Tachikawa, E., Kudo, K., Harada, K., Kashimoto, T., Miyate, Y., Kakizaki, A., and Takahashi, E. Effects of ginseng saponins on responses induced by various receptor stimuli.Eur. J. Pharmacal., 369, 23–32 (1999).
Whiting, P. J., McKernan, R. M., Wafford, K. A. Structure and pharmacology of vertebrate GABA-A receptor subtypes.Int. Rev. Neurobiol., 38, 95–138 (1995)