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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.
Carroll,
NMDA-receptor trafficking and targeting: implications for synaptic transmission and plasticity.
2002, Pubmed
Carroll,
NMDA-receptor trafficking and targeting: implications for synaptic transmission and plasticity.
2002,
Pubmed Castilla-Ortega,
Aggravation of chronic stress effects on hippocampal neurogenesis and spatial memory in LPA₁ receptor knockout mice.
2011,
Pubmed Chun,
International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid receptor nomenclature.
2010,
Pubmed Dubin,
Lysophosphatidic acid stimulates neurotransmitter-like conductance changes that precede GABA and L-glutamate in early, presumptive cortical neuroblasts.
1999,
Pubmed Dubin,
Diversity of lysophosphatidic acid receptor-mediated intracellular calcium signaling in early cortical neurogenesis.
2010,
Pubmed Durand,
Splice variants of the N-methyl-D-aspartate receptor NR1 identify domains involved in regulation by polyamines and protein kinase C.
1993,
Pubmed
,
Xenbase Fernández de Sevilla,
The muscarinic long-term enhancement of NMDA and AMPA receptor-mediated transmission at Schaffer collateral synapses develop through different intracellular mechanisms.
2010,
Pubmed Hecht,
Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex.
1996,
Pubmed Heo,
An open-label trial of Korean red ginseng as an adjuvant treatment for cognitive impairment in patients with Alzheimer's disease.
2008,
Pubmed Hollmann,
Cloned glutamate receptors.
1994,
Pubmed Hwang,
Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, attenuates Alzheimer's disease-related neuropathies: involvement of non-amyloidogenic processing.
2012,
Pubmed Hwang,
Gintonin, newly identified compounds from ginseng, is novel lysophosphatidic acids-protein complexes and activates G protein-coupled lysophosphatidic acid receptors with high affinity.
2012,
Pubmed Jones,
PKC site mutations reveal differential modulation by insulin of NMDA receptors containing NR2A or NR2B subunits.
2005,
Pubmed
,
Xenbase Kennedy,
Improved cognitive performance in human volunteers following administration of guarana (Paullinia cupana) extract: comparison and interaction with Panax ginseng.
2004,
Pubmed Kim,
Protective effects of ginseng saponins on 3-nitropropionic acid-induced striatal degeneration in rats.
2005,
Pubmed Kimura,
Two novel Xenopus homologs of mammalian LP(A1)/EDG-2 function as lysophosphatidic acid receptors in Xenopus oocytes and mammalian cells.
2001,
Pubmed
,
Xenbase Lee,
Panax ginseng enhances cognitive performance in Alzheimer disease.
2008,
Pubmed Lee,
Inhibition of hexokinase leads to neuroprotection against excitotoxicity in organotypic hippocampal slice culture.
2011,
Pubmed Liao,
Evidence for direct protein kinase-C mediated modulation of N-methyl-D-aspartate receptor current.
2001,
Pubmed
,
Xenbase Lisman,
Mechanisms of CaMKII action in long-term potentiation.
2012,
Pubmed MacDonald,
Hippocampal long-term synaptic plasticity and signal amplification of NMDA receptors.
2006,
Pubmed Matas-Rico,
Deletion of lysophosphatidic acid receptor LPA1 reduces neurogenesis in the mouse dentate gyrus.
2008,
Pubmed Moon,
The multi-herbal medicine Gongjin-dan enhances memory and learning tasks via NGF regulation.
2009,
Pubmed Moriyoshi,
Molecular cloning and characterization of the rat NMDA receptor.
1991,
Pubmed
,
Xenbase Ohta,
Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors.
2003,
Pubmed Persson,
The memory-enhancing effects of Ginseng and Ginkgo biloba in healthy volunteers.
2004,
Pubmed Shimono,
Long-term recording of LTP in cultured hippocampal slices.
2002,
Pubmed Steidl,
The adult rat hippocampal slice revisited with multi-electrode arrays.
2006,
Pubmed Stoppini,
A simple method for organotypic cultures of nervous tissue.
1991,
Pubmed Timofeeva,
Glutamate and nicotinic receptor interactions in working memory: importance for the cognitive impairment of schizophrenia.
2011,
Pubmed Veloso,
Distribution of lipids in human brain.
2011,
Pubmed Zheng,
Ca2+ influx amplifies protein kinase C potentiation of recombinant NMDA receptors.
1997,
Pubmed
,
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