Effects of ginsenoside Rg2 on human neuronal nicotinic acetylcholine receptors
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 Rg(2) has been shown to block the nicotinic acetylcholine receptors in bovine chromaffin cells. We have studied the effect of Rg(2) on different types of human neuronal nicotinic acetylcholine receptors (nAChRs), both homomeric and heteromeric, expressed in Xenopus oocytes. Rg(2) did not affect the acetylcholine (ACh)-induced currents in alpha(7) human receptors, however Rg(2) affected the peak currents, and mainly the desensitization of heteromeric receptors alpha(3)beta(4), alpha(3)beta(2), alpha(4)beta(4), and alpha(4)beta(2). 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 alpha(3)beta(4) and alpha(4)beta(2) receptors where we found a negligible shift in the ACh dose-response curves and a persistence of the Rg(2) 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 Rg(2) does not act as an open channel blocker of human nAChR. The results indicate that Rg(2) 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.
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Cites
Attele, A. S., Wu, J. A., & Yuan, C. (1999) · Biochemical Pharmacology · doi:10.1016/s0006-2952(99)00212-9 · Cited by 1,870 · see citing works
Functional messenger RNAs are produced by SP6 <i>in vitro</i> transcription of cloned cDNAs
Krieg, P. A., & Melton, D. A. (1984) · Nucleic Acids Research · doi:10.1093/nar/12.18.7057 · Cited by 1,533 · see citing works
Picciotto, M. R., Zoli, M., Rimondini, R., Léna, C., Marubio, L. M., Pich, E. M., Fuxe, K., & Changeux, J.-P. (1998) · Nature · doi:10.1038/34413 · Cited by 1,320 · see citing works
Neuronal nicotinic receptors in the human brain
Paterson, D., & Nordberg, A. K. (2000) · Progress in Neurobiology · doi:10.1016/s0301-0082(99)00045-3 · Cited by 782 · see citing works
Nicotinic receptors in the brain: correlating physiology with function
Jones, S., Sudweeks, S. N., & Yakel, J. L. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01471-x · Cited by 447 · see citing works
Timing and Location of Nicotinic Activity Enhances or Depresses Hippocampal Synaptic Plasticity
Ji, D., Lape, R., & Dani, J. A. (2001) · Neuron · doi:10.1016/s0896-6273(01)00332-4 · Cited by 419 · see citing works
Chavez-Noriega, L. E., Crona, J. H., Washburn, M. S., Urrutia, A., Elliott, K. J., & Johnson, E. C. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)36376-1 · Cited by 405 · see citing works
Chavez-Noriega, L. E., Crona, J. H., Washburn, M. S., Urrutia, A., Elliott, K. J., & Johnson, E. C. (1997) · PubMed · Cited by 392 · see citing works
[16] Electrophysiologic recordings from Xenopus oocytes
Stühmer, W. (1998) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(98)93019-1 · Cited by 358 · see citing works
Abnormal Regulation of High Affinity Nicotinic Receptors in Subjects with Schizophrenia
Breese, C. R. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00121-4 · Cited by 343 · see citing works
Gerzanich, V., Wang, F., Kuryatov, A., & Lindstrom, J. M. (1998) · PubMed · Cited by 242 · see citing works
Ochoa, E. L. M., Chattopadhyay, A., & McNamee, M. G. (1989) · Cellular and Molecular Neurobiology · doi:10.1007/bf00713026 · Cited by 206 · see citing works
Open-Channel Blockers at the Human α4β2 Neuronal Nicotinic Acetylcholine Receptor
Buisson, B., & Bertrand, D. (1998) · Molecular Pharmacology · doi:10.1124/mol.53.3.555 · Cited by 179 · see citing works
Neuronal nicotinic receptors: from structure to function
Bertrand, D. (2001) · Nicotine & Tobacco Research · doi:10.1080/14622200110050213 · Cited by 175 · see citing works
Nah, S. Y., Park, H. J., & McCleskey, E. W. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.19.8739 · Cited by 137 · see citing works
Self-citationGerzanich, V., Wang, F., Kuryatov, A., & Lindstrom, J. M. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37589-5 · Cited by 129 · see citing works
Competitive Neuronal Nicotinic Receptor Antagonists: A New Direction for Drug Discovery
Dwoskin, L. P., & Crooks, P. A. (2001) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29396-4 · Cited by 125 · see citing works
Albuquerque, E. X., Pereira, E. F. R., Mike, Á., Eisenberg, H. M., Maelicke, A., & Alkondon, M. (2000) · Behavioural Brain Research · doi:10.1016/s0166-4328(00)00208-4 · Cited by 95 · see citing works
Stauderman, K. A., Mahaffy, L. S., AKONG, M., Veliçelebi, G., Chavez-Noriega, L. E., Crona, J. H., Johnson, E. C., Elliott, K. J., Gillespie, A. J., Reid, R. T., et al. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37270-2 · Cited by 90 · see citing works
Stauderman, K. A., Mahaffy, L. S., Akong, M., Veliçelebi, G., Chavez-Noriega, L. E., Crona, J. H., Johnson, E. C., Elliott, K. J., Gillespie, A., Reid, R. T., et al. (1998) · PubMed · doi:10.7270/q28g8j7q · Cited by 86 · see citing works
Effects of ginsenosides on Ca2 channels and membrane capacitance in rat adrenal chromaffin cells
Kim, H.-S., Lee, J.-H., Goo, Y., & Nah, S.-Y. (1998) · Brain Research Bulletin · doi:10.1016/s0361-9230(98)00014-8 · Cited by 68 · see citing works
Self-citationVoltage-dependent inhibition of brain Na (+) channels by American ginseng
Liu, D., Li, B., Liu, Y., Attele, A. S., Kyle, J. W., & Yuan, C.-S. (2001) · European Journal of Pharmacology · doi:10.1016/s0014-2999(01)00735-x · Cited by 63 · see citing works
Tachikawa, E., Kudo, K., Kashimoto, T., et al. (1995) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)09519-9 · Cited by 63 · see citing works
Nicotinic receptor subtypes in human brain related to aging and dementia
Perry, E. K., Martin-Ruiz, C. M., & COURT, J. A. (2001) · Alcohol · doi:10.1016/s0741-8329(01)00130-6 · Cited by 62 · see citing works
Effect of ginsenosides, active components of ginseng, on capsaicin-induced pain-related behavior
Nah, J., Hahn, J., Chung, S., et al. (2000) · Neuropharmacology · doi:10.1016/s0028-3908(00)00048-4 · Cited by 56 · see citing works
Drugs selective for nicotinic receptor subtypes: a real possibility or a dream?
Gotti, C., Carbonnelle, E., Moretti, M., Zwart, R., & Clementi, F. (2000) · Behavioural Brain Research · doi:10.1016/s0166-4328(00)00212-6 · Cited by 55 · see citing works
Chiodini, F., Charpantier, E., Müller, D., et al. (2001) · Anesthesiology · doi:10.1097/00000542-200104000-00019 · Cited by 51 · see citing works
Li, Z., Guo, Y. Y., Wu, C., et al. (1999) · Journal of Pharmacy and Pharmacology · doi:10.1211/0022357991772484 · Cited by 49 · see citing works
Choi, S., Rho, S., Jung, S., et al. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703856 · Cited by 48 · see citing works
Self-citationCovernton, P. J. O., & Connolly, J. G. (2000) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(99)00185-5 · Cited by 47 · see citing works
Bohler, S., Gay, S., Bertrand, S., Corringer, P. J., Edelstein, S. J., Changeux, J., & Bertrand, D. (2001) · Biochemistry · doi:10.1021/bi0020022 · Cited by 41 · see citing works
Herrero, C. J., García‐Palomero, E., Pintado, A. J., et al. (1999) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702692 · Cited by 39 · see citing works
Activation and Ca2+Permeation of Stably Transfected α3/β4 Neuronal Nicotinic Acetylcholine Receptor
Zhang, J., Xiao, Y., Abdrakhmanova, G., et al. (1999) · Molecular Pharmacology · doi:10.1124/mol.55.6.970 · Cited by 37 · see citing works
Fujimoto, K., Sakata, T., Ishimaru, T., et al. (1989) · Psychopharmacology · doi:10.1007/bf00442819 · Cited by 31 · see citing works
Acute and chronic effects of ginseng saponins on maternal aggression in mice
Yoshimura, H., Watanabe, K., & Ogawa, N. (1988) · European Journal of Pharmacology · doi:10.1016/0014-2999(88)90013-1 · Cited by 26 · see citing works
Tachikawa, E., Kudo, K., Nunokawa, M., Kashimoto, T., Takahashi, E., & Kitagawa, S. (2001) · Biochemical Pharmacology · doi:10.1016/s0006-2952(01)00743-2 · Cited by 23 · see citing works
Kim, H.-S., & Kim, K.-S. (1999) · Behavioural Brain Research · doi:10.1016/s0166-4328(99)00030-3 · Cited by 21 · see citing works
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Kim, S., Ahn, K., Oh, T. H., Nah, S.-Y., & Rhim, H. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00870-7 · Cited by 128 · see citing works
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- Authors
- Sala, F., Mulet, J., Choi, S., Jung, S.-Y., Nah, S.-Y., Rhim, H., Valor, L. M., Criado, M., & Sala, S.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- ORCID
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2002-06
- Volume
- 301
- Issue
- 3
- Pages
- 1052-1059
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2126352957
- Cited by
- 80
- References
- 37
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 1 · 2012: 2
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ginseng Biological Effects and Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- ginsenoside Rg2, ginsenosides, neuronal nicotinic acetylcholine receptors, alpha4beta2 receptor, receptor desensitization, non-competitive antagonism, acetylcholine-induced currents
- MeSH terms
- Animals, Dose-Response Relationship, Drug, Genetic Vectors, Panax, Humans, Ion Channels, Membrane Potentials, Oocytes, Receptors, Nicotinic, Saponins, Transfection, Xenopus, Patch-Clamp Techniques, Ginsenosides
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