title: Electrophysiological characterization of methyleugenol: a novel agonist of GABA(A) receptors.
abstract: Methyleugenol (ME) is a natural constituent isolated from many plant essential oils having multiple biological effects including anticonvulsant and anesthetic activities, although the underlying mechanisms remain unclear. Here, we identify ME as a novel agonist of ionotropic γ-aminobutyric acid (GABA) receptors. At lower concentrations (∼30 μM), ME significantly sensitized GABA-induced, but not glutamate- or glycine-induced, currents in cultured hippocampal neurons, indicative of a preferentially modulatory role of this compound for A type GABA receptors (GABAARs). In addition, ME at higher concentrations (≥100 μM) induced a concentration-dependent, Cl(-)-permeable current in hippocampal neurons, which was inhibited by a GABAAR channel blocker, picrotoxin, and a competitive GABAAR antagonist, bicuculline, but not a specific glycine receptor inhibitor, strychnine. Moreover, ME activated a similar current mediated by recombinant α1-β2-γ2 or α5-β2-γ2 GABAARs in human embryonic kidney (HEK) cells. Consequently, ME produced a strong inhibition of synaptically driven neuronal excitation in hippocampal neurons. Together, these results suggest that ME represents a novel agonist of GABAARs, shedding additional light on future development of new therapeutics targeting GABAARs. The present study also adds GABAAR activation to the list of molecular targets of ME that probably account for its biological activities.
authors: Department of Developmental and Behavioral Pediatrics, Shanghai Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Shanghai Jiao Tong University School of Medicine , Shanghai 200129, China.
authors: Jing
authors: J
authors: Ding
authors: Chen
authors: C
authors: Huang
authors: Zhong
authors: Z
authors: Peng
authors: Yuxuan
authors: Y
authors: Xie
authors: Shining
authors: S
authors: Deng
authors: Yan-Zhen
authors: YZ
authors: Nie
authors: Tian-Le
authors: TL
authors: Xu
authors: Wei-Hong
authors: WH
authors: Ge
authors: Wei-Guang
authors: WG
authors: Li
authors: Fei
authors: F
authors: Li
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005054:Eugenol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D058785:GABA-A Receptor Agonists / Q000737:chemistry* / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D018682:GABA Agents; D058785:GABA-A Receptor Agonists; C005223:methyleugenol; D018698:Glutamic Acid; D005054:Eugenol; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine; D005998:Glycine
keywords: GABA; GABAA receptor; Methyleugenol; neuronal excitability