Differential effect of ginsenoside metabolites on the 5-HT3A receptor-mediated ion current in Xenopus oocytes.
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.
Lee
Byung-Hwan
BH
Research Laboratory for the Study of Ginseng Signal Transduction and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Korea.
Jeong
Sang Min
SM
Lee
Jun-Ho
JH
Kim
Dong-Hyun
DH
Kim
Jong-Hoon
JH
Kim
Jai-Il
JI
Shin
Ho-Chul
HC
Lee
Sang-Mok
SM
Nah
Seung-Yeol
SY
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
D018076:DNA, Complementary; D036145:Ginsenosides; D007477:Ions; D018075:RNA, Complementary; D044406:Receptors, Serotonin, 5-HT3; C112772:ginsenoside compound K