PMID- 25635877
OWN - NLM
STAT- MEDLINE
DCOM- 20160113
LR  - 20240109
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 1
DP  - 2015
TI  - Eugenol inhibits the GABAA current in trigeminal ganglion neurons.
PG  - e0117316
LID - 10.1371/journal.pone.0117316 [doi]
LID - e0117316
AB  - 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 alpha1beta2gamma2 
      subtype using the whole-cell patch clamp technique. RT-PCR and Western blot 
      analysis were used to confirm the expression of GABAA receptor gamma2 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 alpha1beta2gamma2 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.
FAU - Lee, Sang Hoon
AU  - Lee SH
AD  - Department of Biomedical Science, Graduate School of Biomedical Science; 
      Engineering, Hanyang University, Seoul, Republic of Korea.
FAU - Moon, Jee Youn
AU  - Moon JY
AD  - Department of Anesthesiology and Pain Medicine, Seoul National University 
      Hospital College of Medicine, Seoul, Republic of Korea.
FAU - Jung, Sung Jun
AU  - Jung SJ
AD  - Department of Physiology, Medical School, Hanyang University, Seoul, Republic of 
      Korea.
FAU - Kang, Jin Gu
AU  - Kang JG
AD  - Department of Anaesthesiology and Pain Medicine, Hallim University, Dongtan 
      Sacred Heart Hospital, Kyunggi-do, Republic of Korea.
FAU - Choi, Seung Pyo
AU  - Choi SP
AD  - Department of Anesthesiology and Pain Medicine, Seoul National University 
      Hospital College of Medicine, Seoul, Republic of Korea.
FAU - Jang, Jun Ho
AU  - Jang JH
AD  - Department of Biomedical Science, Graduate School of Biomedical Science; 
      Engineering, Hanyang University, Seoul, Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150130
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Receptors, GABA-A)
RN  - 3T8H1794QW (Eugenol)
SB  - IM
MH  - Animals
MH  - Eugenol/*pharmacology
MH  - HEK293 Cells
MH  - Humans
MH  - Ion Channel Gating/*drug effects
MH  - Male
MH  - Neurons/drug effects/*metabolism
MH  - Rats, Sprague-Dawley
MH  - Receptors, GABA-A/*metabolism
MH  - Trigeminal Ganglion/*metabolism
PMC - PMC4311912
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/01/31 06:00
MHDA- 2016/01/14 06:00
PMCR- 2015/01/30
CRDT- 2015/01/31 06:00
PHST- 2014/06/29 00:00 [received]
PHST- 2014/12/20 00:00 [accepted]
PHST- 2015/01/31 06:00 [entrez]
PHST- 2015/01/31 06:00 [pubmed]
PHST- 2016/01/14 06:00 [medline]
PHST- 2015/01/30 00:00 [pmc-release]
AID - PONE-D-14-29052 [pii]
AID - 10.1371/journal.pone.0117316 [doi]
PST - epublish
SO  - PLoS One. 2015 Jan 30;10(1):e0117316. doi: 10.1371/journal.pone.0117316. 
      eCollection 2015.