title: Differential effect of ginsenoside metabolites on the 5-HT3A receptor-mediated ion current in Xenopus oocytes.
abstract: Ginsenosides are major active ingredients of Panax ginseng. They have a number of pharmacological and physiological actions and are transformed into compound K (CK) or M4 by intestinal microorganisms. CK is derived from protopanaxadiol (PD) ginsenosides, whereas M4 is derived from protopanaxatriol (PT) ginsenosides. Recent reports show that ginsenosides act as pro-drugs for these metabolites. In previous work we demonstrated that the ginsenoside Rg2 regulates human 5-hydroxytryptamine3A (5-HT3A) receptor channel activity [Choi et al. (2003)]. In the present study, we investigated the effect of CK and M4 on the activity of the human 5-HT3A receptor channel. The 5-HT3A receptor was expressed in Xenopus oocytes, and the current was measured using the two-electrode voltage clamp technique. Treatment with CK or M4 had no effect on oocytes injected with 5-HT3A receptor cRNA. However pretreatment with M4 or CK followed by injection of 5-HT3A receptor cRNA led to reversible inhibition of the 5-HT-induced inward peak current (I(5-HT)). Half maximal inhibitory concentrations (IC50) of CK and M4 were 36.9 +/- 9.6 and 7.3 +/- 2.2 microM, respectively. Inhibition by M4 was non-competitive and voltage-independent. These results indicate that M4, a metabolite of PT ginsenosides, acts primarily on 5-HT3A receptors and further, that ginsenosides as well as ginsenoside metabolites can influence 5-HT3A receptor channel activity in Xenopus oocytes.
authors.affiliation: Research Laboratory for the Study of Ginseng Signal Transduction and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Korea.
authors.forename: Byung-Hwan
authors.initials: BH
authors.lastname: Lee
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Jeong
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Jai-Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Ho-Chul
authors.initials: HC
authors.lastname: Shin
authors.forename: Sang-Mok
authors.initials: SM
authors.lastname: Lee
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
mesh_terms: D000818:Animals; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D036145:Ginsenosides / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007413:Intestinal Mucosa / Q000378:metabolism; D007477:Ions; D008956:Models, Chemical; D009865:Oocytes / Q000378:metabolism*; D005894:Panax / Q000378:metabolism; D018408:Patch-Clamp Techniques; D018075:RNA, Complementary / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D014981:Xenopus
chemical_list: D018076:DNA, Complementary; D036145:Ginsenosides; D007477:Ions; D018075:RNA, Complementary; D044406:Receptors, Serotonin, 5-HT3; C112772:ginsenoside compound K