Choi, Sun-Hye Kim, Hyeon-Joong Kim, Bo-Ra Shin, Tae-Joon Hwang, Sung-Hee Lee, Byung-Hwan Lee, Sang-Mok Rhim, Hyewhon Nah, Seung-Yeol 2024-01-20T13:02:29Z 2024-01-20T13:02:29Z 2021-09-01 2013-02 1016-8478 https://pubs.kist.re.kr/handle/201004/128394 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 (P2X(1)-P2X(7)) have been identified. Most of the P2X(1) receptors are expressed in the smooth muscles of genitourinary organs involved in reproduction. A main characteristic of the P2X(1) receptor is rapid desensitization after repeated ATP treatment of cells or tissues expressing P2X(1) receptors. In the present study, we examined the effect of gintonin on P2X(1) receptor channel activity. P2X(1) receptors were heterologously expressed in Xenopus oocytes. ATP treatment of oocytes expressing P2X(1) receptors induced large inward currents (I (ATP) ), but repetitive ATP treatments induced a rapid desensitization of I (ATP) . Gintonin treatment after P2X(1) 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 P2X(1) 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 P2X(1) receptor through a phosphoinositide-dependent pathway. English KOREAN SOC MOLECULAR & CELLULAR BIOLOGY XENOPUS OOCYTES DESENSITIZATION ACTIVATION PHYSIOLOGY Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, potentiates ATP-gated P2X(1) receptor channel currents Article 10.1007/s10059-013-2293-x 1 MOLECULES AND CELLS, v.35, no.2, pp.142 - 150 MOLECULES AND CELLS 35 2 142 150 scie scopus kci ART001742559 000315582300008 2-s2.0-84879624218 Biochemistry & Molecular Biology Cell Biology Biochemistry & Molecular Biology Cell Biology Article XENOPUS OOCYTES DESENSITIZATION ACTIVATION PHYSIOLOGY gintonin LPA receptor P2X(1) receptor P2X(1) receptor potentiation