title: Gintonin, a ginseng-derived novel ingredient, evokes long-term potentiation through N-methyl-D-aspartic acid receptor activation: involvement of LPA receptors.
abstract: Ginseng has been shown to have memory-improving effects in human. However, little is known about the active components and the molecular mechanisms underlying its effects. Recently, we isolated novel lysophosphatidic acids (LPAs)-ginseng protein complex derived from ginseng, gintonin. Gintonin activates G protein-coupled LPA receptors with high affinity. Gintonin activated Ca²⁺-activated Clchannels in Xenopus oocytes through the activation of endogenous LPA receptor. In the present study, we investigated whether the activation of LPA receptor by gintonin is coupled to the regulation of N-methyl-D-aspartic acid (NMDA) receptor channel activity in Xenopus oocytes expressing rat NMDA receptors. The NMDA receptor-mediated ion current (I ( NMDA )) was measured using the two-electrode voltage-clamp technique. In oocytes injected with cRNAs encoding NMDA receptor subunits, gintonin enhanced I ( NMDA ) in a concentration-dependent manner. Gintonin-mediated I ( NMDA ) enhancement was blocked by Ki16425, an LPA1/3 receptor antagonist. Gintonin action was blocked by a PLC inhibitor, IP₃ receptor antagonist, Ca²⁺ chelator, and a tyrosine kinase inhibitor. The site-directed mutation of Ser1308 of the NMDA receptor, which is phosphorylated by protein kinase C (PKC), to an Ala residue, or co-expression of receptor protein tyrosine phosphatase with the NMDA receptor attenuated gintonin action. Moreover, gintonin treatment elicited a transient elevation of [Ca²⁺](i) in cultured hippocampal neurons and elevated longterm potentiation (LTP) in both concentration-dependent manners in rat hippocampal slices. Gintonin-mediated LTP induction was abolished by Ki16425. These results indicate that gintonin-mediated I ( NMDA ) potentiation and LTP induction in the hippocampus via the activation of LPA receptor might be responsible for ginseng-mediated improvement of memory-related brain functions.
authors.affiliation: Department of Physiology, College of Veterinary Medicine and Veterinary Science Research Institute, and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea.
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Shin
authors.forename: Hyeon-Joong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Byeong-Jae
authors.initials: BJ
authors.lastname: Kwon
authors.forename: Sun-Hye
authors.initials: SH
authors.lastname: Choi
authors.forename: Hyun-Bum
authors.initials: HB
authors.lastname: Kim
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Hwang
authors.forename: Byung-Hwan
authors.initials: BH
authors.lastname: Lee
authors.forename: Sang-Mok
authors.initials: SM
authors.lastname: Lee
authors.forename: R Suzanne
authors.initials: RS
authors.lastname: Zukin
authors.forename: Ji-Ho
authors.initials: JH
authors.lastname: Park
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
authors.forename: Joon-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D017774:Long-Term Potentiation; D008246:Lysophospholipids / Q000494:pharmacology*; D008564:Membrane Potentials; D009474:Neurons / Q000378:metabolism; D005894:Panax / Q000737:chemistry*; D018408:Patch-Clamp Techniques; D010940:Plant Proteins / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D014981:Xenopus / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D010940:Plant Proteins; D049368:Receptors, Lysophosphatidic Acid; D016194:Receptors, N-Methyl-D-Aspartate; D011493:Protein Kinase C; D002118:Calcium