title: Direct activation of GABAA receptors by substances in the organic acid fraction of Japanese sake.
abstract: We investigated the effect of substances present in Japanese sake on the response of ionotropic γ-aminobutyric acid (GABA)A receptors expressed in Xenopus oocytes. Sake was fractionated by ion-exchange chromatography. The fraction containing organic acids (OA fraction) showed agonist activities on the GABAA receptor. OA fractions from sake were analyzed by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Of the 64 compounds identified, 13 compounds showed GABAA receptor agonist activities. Especially, l-lactic acid showed high agonist activity and its EC50 value was 37μM. Intraperitoneal injections of l-lactic acid, gluconic acid, and pyruvic acid (10, 10, and 5mg/kg BW, respectively), which showed agonistic activity on the GABAA receptor, led to significant anxiolytic effects during an elevated plus-maze test in mice.
authors: National Research Institute of Brewing, Higashi-hiroshima, Japan.
authors: Hanae
authors: H
authors: Izu
authors: Department of Biotechnology and Chemistry, Faculty of Engineering, Kindai University, Higashi-hiroshima, Hiroshima 739-2116, Japan.
authors: Kensuke
authors: K
authors: Shigemori
authors: Department of Biotechnology and Chemistry, Faculty of Engineering, Kindai University, Higashi-hiroshima, Hiroshima 739-2116, Japan.
authors: Masaya
authors: M
authors: Eguchi
authors: Department of Biotechnology and Chemistry, Faculty of Engineering, Kindai University, Higashi-hiroshima, Hiroshima 739-2116, Japan.
authors: Shuhei
authors: S
authors: Kawane
authors: Department of Biotechnology and Chemistry, Faculty of Engineering, Kindai University, Higashi-hiroshima, Hiroshima 739-2116, Japan.
authors: Shouko
authors: S
authors: Fujii
authors: Department of Biotechnology and Chemistry, Faculty of Engineering, Kindai University, Higashi-hiroshima, Hiroshima 739-2116, Japan.
authors: Yuji
authors: Y
authors: Kitamura
authors: Applied Molecular Bioscience, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
authors: Hitoshi
authors: H
authors: Aoshima
authors: Department of Biotechnology and Chemistry, Faculty of Engineering, Kindai University, Higashi-hiroshima, Hiroshima 739-2116, Japan. Electronic address: y-yamada@hiro.kindai.ac.jp.
authors: Yasue
authors: Y
authors: Yamada
mesh_terms: D000434:Alcoholic Beverages / Q000032:analysis*; D000818:Animals; D002852:Chromatography, Ion Exchange; D005260:Female; D058785:GABA-A Receptor Agonists / Q000494:pharmacology*; D019344:Lactic Acid / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D019344:Lactic Acid
keywords: Agonist; Ionotropic γ-aminobutyric acid receptor; Organic acid; Sake