ⓒ The Korean Society of Ginseng 55 http://ginsengres.org pISSN: 1226-8453 eISSN: 2093-4947 Research Article J. Ginseng Res. Vol. 36, No. 1, 55-60 (2012) http://dx.doi.org/10.5142/jgr.2012.36.1.55 E-mail: synah@konkuk.ac.kr Tel: +82-2-450-4154, Fax: +82-2-450-3037 * Corresponding author INTRODUCTION Gamma-aminobutyric acid (GABA) receptor A (GA- BA A ) receptors are members of the large ‘Cys-loop’ super-family of evolutionarily related and structurally similar ligand-gated ion channels that also includes the nicotinic acetylcholine, glycine, and 5-HT 3 receptors [1]. The GABA receptor is predominantly expressed in the central nervous system [2,3], and forms a chloride- selective transmembrane channel in the post-synaptic sites of nerve terminals. Thus, the GABA A receptor is responsible for fast inhibitory synaptic transmission [4,5]. Recent biochemical binding assays produced evidence that ginsenosides might regulate the GABA A receptor. For example, Kimura et al. [6] showed that ginsenosides differentially regulate [ 3 H]-f1unitrazepam or [ 3 H]-musci- mol binding to the GABA A receptor in a rat brain mem- brane fraction. Kim et al. [7] reported that prolonged in- fusion with ginsenoside Rc, but not ginsenoside Rg 1 , into rat brain elevates [ 3 H]-muscimol binding to the GABA A receptor in a brain region-specific manner. Thus, gin- senosides may regulate the GABA A receptor by affect- ing ligand affinity for its receptor, but there is no direct evidence on the regulation of GABA A receptor channel activity by ginsenosides. On the other hand, Choi et al . [8] showed that ginsenoside Rc enhances GABA-mediated Effects of Ginsenoside Metabolites on GABA A Receptor-Mediated Ion Currents Byung-Hwan Lee 1 , Sun-Hye Choi 1 , Tae-Joon Shin 1 , Sung-Hee Hwang 1 , Jiyeon Kang 1 , Hyeon-Joong Kim 1 , Byung-Ju Kim 2 , and Seung-Yeol Nah 1* 1 Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea 2 Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870, Korea In a previous report, we demonstrated that ginsenoside Rc, one of major ginsenosides from Panax ginseng, enhances γ-aminobutyric acid (GABA) receptor A (GABA A )-mediated ion channel currents. However, little is known about the effects of ginsenoside metabolites on GABA A receptor channel activity. The present study investigated the effects of ginsenoside metabolites on human recombinant GABA A receptor (α 1 β 1 γ 2s ) channel activity expressed in Xenopus oocytes using a two-electrode voltage clamp technique. M4, a metabolite of protopanaxatriol ginsenosides, more potently inhibited the GABA-induced inward peak current (I GABA ) than protopanaxadiol (PPD), a metabolite of PPD ginsenosides. The effect of M4 and PPD on I GABA was both concentration-dependent and reversible. The half-inhibitory concentration (IC 50 ) values of M4 and PPD were 17.1±2.2 and 23.1±8.6 µM, respectively. The inhibition of I GABA by M4 and PPD was voltage-independent and non-competitive. This study implies that the regulation of GABA A receptor channel activity by ginsenoside metabolites differs from that of ginsenosides. Keywords: Panax ginseng, Ginsenoside metabolites, Gamma-aminobutyric acid receptor A receptor, Xenopus oocytes This is an Open Access article distributed under the terms of the Cre- ative Commons Attribution Non-Commercial License (http://creativecom- mons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Received 14 Oct. 2011, Revised 05 Dec. 2011, Accepted 05 Dec. 2011