title: Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, potentiates ATP-gated P2X₁ receptor channel currents.
abstract: Ginseng, the root of Panax ginseng C.A. Meyer, is used as a general tonic. Recently, we isolated a novel ginsengderived lysophosphatidic acid (LPA) receptor ligand, gintonin. Gintonin activates G protein-coupled LPA receptors with high affinity in cells endogenously expressing LPA receptors, e.g., Xenopus oocytes. P2X receptors are ligandgated ion channels activated by extracellular ATP, and 7 receptor subtypes (P2X1-P2X7) have been identified. Most of the P2X1 receptors are expressed in the smooth muscles of genitourinary organs involved in reproduction. A main characteristic of the P2X1 receptor is rapid desensitization after repeated ATP treatment of cells or tissues expressing P2X1 receptors. In the present study, we examined the effect of gintonin on P2X1 receptor channel activity. P2X1 receptors were heterologously expressed in Xenopus oocytes. ATP treatment of oocytes expressing P2X1 receptors induced large inward currents (I ATP ), but repetitive ATP treatments induced a rapid desensitization of I ATP . Gintonin treatment after P2X1 receptor desensitization potentiated I ATP in a concentration-dependent manner. We further examined the signaling transduction pathways involved in gintonin-mediated potentiation of I ATP . Gintoninmediated I ATP potentiation was blocked by Ki16425, an LPA1/3 receptor antagonist, a PKC inhibitor, a PLC inhibitor, and a PI4-Kinase inhibitor but not by a calcium chelator. In addition, mutations of the phosphoinositide binding site of the P2X1 receptor greatly attenuated the gintonin-mediated I ATP potentiation. These results indicate that G protein-coupled LPA receptor activation by gintonin is coupled to the potentiation of the desensitized P2X1 receptor through a phosphoinositide-dependent pathway.
authors: Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea.
authors: Sun-Hye
authors: SH
authors: Choi
authors: Hyeon-Joong
authors: HJ
authors: Kim
authors: Bo-Ra
authors: BR
authors: Kim
authors: Tae-Joon
authors: TJ
authors: Shin
authors: Sung-Hee
authors: SH
authors: Hwang
authors: Byung-Hwan
authors: BH
authors: Lee
authors: Sang-Mok
authors: SM
authors: Lee
authors: Hyewhon
authors: H
authors: Rhim
authors: Seung-Yeol
authors: SY
authors: Nah
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D007555:Isoxazoles / Q000494:pharmacology; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000378:metabolism; D005894:Panax / Q000737:chemistry*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism*; D058474:Receptors, Purinergic P2X1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000077191:Wortmannin; D014982:Xenopus laevis / Q000378:metabolism
chemical_list: C477898:3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) benzylsulfanyl) propanoic acid; D000730:Androstadienes; D004963:Estrenes; D007555:Isoxazoles; D010716:Phosphatidylinositols; D010936:Plant Extracts; D011422:Propionates; D011760:Pyrrolidinones; D049368:Receptors, Lysophosphatidic Acid; D058474:Receptors, Purinergic P2X1; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D000255:Adenosine Triphosphate; D000077191:Wortmannin