title: Eugenol inhibits the GABAA current in trigeminal ganglion neurons.
abstract: Eugenol has sedative, antioxidant, anti-inflammatory, and analgesic effects, but also serves as an irritant through the regulation of a different set of ion channels. Activation of gamma aminobutyric acid (GABA) receptors on sensory neurons leads to the stabilization of neuronal excitability but contributes to formalin-induced inflammatory pain. In this study, we examined the effect of eugenol on the GABA-induced current in rat trigeminal ganglia (TG) neurons and in human embryonic kidney (HEK) 293 cells expressing the GABAA receptor α1β2γ2 subtype using the whole-cell patch clamp technique. RT-PCR and Western blot analysis were used to confirm the expression of GABAA receptor γ2 subunit mRNA and protein in the TG and hippocampus. Eugenol decreased the amplitude ratio of the GABA-induced current to 27.5 ± 3.2% (p < 0.05) in TG neurons, which recovered after a 3-min washout. In HEK 293 cells expressing the α1β2γ2 subtype, eugenol inhibited GABA-induced currents in a dose-dependent manner. Application of eugenol also decreased the GABA response in the presence of a G-protein blocker. Eugenol pretreatment with different concentrations of GABA resulted in similar inhibition of the GABA-induced current in a non-competitive manner. In conclusion, eugenol inhibits the GABA-induced current in TG neurons and HEK 293 cells expressing the GABAA receptor in a reversible, dose-dependent, and non-competitive manner, but not via the G-protein pathway. We suggest that the GABAA receptor could be a molecular target for eugenol in the modulation of nociceptive information.
authors: Department of Biomedical Science, Graduate School of Biomedical Science; Engineering, Hanyang University, Seoul, Republic of Korea.
authors: Sang Hoon
authors: SH
authors: Lee
authors: Department of Anesthesiology and Pain Medicine, Seoul National University Hospital College of Medicine, Seoul, Republic of Korea.
authors: Jee Youn
authors: JY
authors: Moon
authors: Department of Physiology, Medical School, Hanyang University, Seoul, Republic of Korea.
authors: Sung Jun
authors: SJ
authors: Jung
authors: Department of Anaesthesiology and Pain Medicine, Hallim University, Dongtan Sacred Heart Hospital, Kyunggi-do, Republic of Korea.
authors: Jin Gu
authors: JG
authors: Kang
authors: Department of Anesthesiology and Pain Medicine, Seoul National University Hospital College of Medicine, Seoul, Republic of Korea.
authors: Seung Pyo
authors: SP
authors: Choi
authors: Department of Biomedical Science, Graduate School of Biomedical Science; Engineering, Hanyang University, Seoul, Republic of Korea.
authors: Jun Ho
authors: JH
authors: Jang
mesh_terms: D000818:Animals; D005054:Eugenol / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000378:metabolism*
chemical_list: D011963:Receptors, GABA-A; D005054:Eugenol
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