Abstract
Ginseng saponins, major active components of ginseng root used by folk medicine in the treatment of various diseases, produce multiple pharmacological responses having many effects on the central and peripheral nervous system. Specifically, ginsenoside Rg2has been shown to block the nicotinic acetylcholine receptors in bovine chromaffin cells. We have studied the effect of Rg2 on different types of human neuronal nicotinic acetylcholine receptors (nAChRs), both homomeric and heteromeric, expressed inXenopus oocytes. Rg2 did not affect the acetylcholine (ACh)-induced currents in α7 human receptors, however Rg2 affected the peak currents, and mainly the desensitization of heteromeric receptors α3β4, α3β2, α4β4, and α4β2. Both effects, a diminution of peak current and an increase of desensitization, are dose-dependent and are very similar for all the receptors. The mechanism of action has been studied in more detail in α3β4 and α4β2receptors where we found a negligible shift in the ACh dose-response curves and a persistence of the Rg2 effects at high ACh concentrations, indicative of a noncompetitive antagonism. A lack of voltage dependence on the reduction of the peak currents induced by ACh also suggests that Rg2 does not act as an open channel blocker of human nAChR. The results indicate that Rg2 acts specifically on heteromeric human nAChRs modulating their desensitization and suggest a possible mechanism by which this saponin contributes to the multiple therapeutic effects of ginseng.
Footnotes
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This work was supported by Grants PM98-0097 from the Ministry of Education of Spain (to F.S.) and PM98-0104 (to M.C.) and by 2000 Ministry of Science and Technology National Research Laboratory Program Grant 2000-N-NL-01-C-180 (to S.-Y.N.). L.M.V. was the recipient of a predoctoral fellowship of Generalitat Valenciana.
- Abbreviations:
- nAChR
- neuronal nicotinic acetylcholine receptor
- ACh
- acetylcholine
- BAPTA
- 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid
- Received December 10, 2001.
- Accepted February 13, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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