title: Gintonin stimulates gliotransmitter release in cortical primary astrocytes.
abstract: Lysophosphatidic acid (LPA) is a simple and minor phospholipid, but serves as a lipid-derived neurotransmitter via activation of G protein-coupled LPA receptors. Astrocytes abundantly express LPA receptors and contain gliotransmitters that modulate astrocyte-neuron interactions. Gintonin is a novel ginseng-derived G protein-coupled LPA receptor ligand. Gintonin induces [Ca(2+)]i transients in neuronal and non-neuronal cells via activation of LPA receptors, which regulate calcium-dependent ion channels and receptors. A line of evidence shows that neurotransmitter-mediated [Ca(2+)]i elevations in astrocytes are coupled with gliotransmitter release. However, little is known about whether gintonin-mediated [Ca(2+)]i transients are coupled to gliotransmitter release in astrocytes. In the present study, we examined the effects of gintonin on adenosine triphosphate (ATP) and glutamate release in mouse cortical primary astrocytes. Application of gintonin to astrocytes induced [Ca(2+)]i transients in a concentration-dependent and reversible manner. However, ginsenosides, other active ingredients in ginseng, had no effect on [Ca(2+)]i transients. The induction of gintonin-mediated [Ca(2+)]i transients was attenuated/blocked by the LPA1/3 receptor antagonist Ki16425, a phospholipase C inhibitor, an inositol 1,4,5-triphosphate receptor antagonist, and an intracellular Ca(2+) chelator. Gintonin treatment on astrocytes increased ATP and glutamate release in a concentration- and time-dependent manner. BAPTA and Ki16425 attenuated gintonin-mediated ATP and glutamate release in astrocytes. The present study shows that gintonin-mediated [Ca(2+)]i transients are coupled to gliotransmitter release via LPA receptor activation. Finally, gintonin-mediated [Ca(2+)]i transients and gliotransmitter release from astrocytes via LPA receptor activation might explain one mechanism of gintonin-mediated neuromodulation in the central nervous system.
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine Konkuk University, Seoul 143-701, South Korea.
authors.forename: Hyunsook
authors.initials: H
authors.lastname: Kim
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine Konkuk University, Seoul 143-701, South Korea.
authors.forename: Byung-Hwan
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine Konkuk University, Seoul 143-701, South Korea.
authors.forename: Sun-Hye
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine Konkuk University, Seoul 143-701, South Korea.
authors.forename: Hyeon-Joong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine Konkuk University, Seoul 143-701, South Korea.
authors.forename: Suk-Won
authors.initials: SW
authors.lastname: Jung
authors.affiliation: Department of Pharmaceutical Engineering, College of Health Sciences, Sangji University, Wonju 220-702, South Korea.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Hwang
authors.affiliation: Center for Neuroscience, Korea Institute of Science and Technology, Seoul 139-791,South Korea.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Rhim
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Hyung-Chun
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Department of Convergence Medical Science, College of Oriental Korean Medicine, Kyung Hee University, Seoul 130-701, South Korea.
authors.forename: Ik-Hyun
authors.initials: IH
authors.lastname: Cho
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine Konkuk University, Seoul 143-701, South Korea. Electronic address: synah@konkuk.ac.kr.
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008246:Lysophospholipids / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D005894:Panax / Q000737:chemistry*; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D004365:Drugs, Chinese Herbal; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; C032881:lysophosphatidic acid; D002118:Calcium
keywords: Astrocytes; Ginseng; Gintonin; Gliotransmitter release; Lysophosphatidic acid receptor; [Ca(2+)](i) transients