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.
Highlights
Eugenol is an aromatic molecule present in various plants and essential oils
We checked expression of the α1β2γ2 subtype, which constitutes 50% of the GABAA receptors, in the trigeminal ganglia (TG) neurons. mRNA encoding GABAA receptor γ2 was detected in the rat TG and hippocampus using RT-PCR
Our results are consistent with a previous study showing that GABAA receptor γ2 subunits are expressed in approximately 90% of TG neurons and that the α1β2γ2 GABAA receptor is the main subtype found in TG neurons [11]
Summary
Eugenol is an aromatic molecule present in various plants and essential oils. Numerous studies have examined the biological activity of eugenol as an antibacterial agent and in the immune, reproductive, cardiovascular, gastric, nervous, and urinary systems [1]. Eugenol has been used extensively in dentistry because of its ability to allay tooth pain [2]; the molecular. Eugenol Inhibits the GABAA Receptor mechanisms of its analgesic action remain largely unexplained. Previous studies have suggested that the inhibition of voltage-gated Na+ and Ca2+ channel currents by eugenol might contribute to its analgesic effects [3,4,5]. Activation of transient receptor potential vanilloid receptor 1 (TRPV1) and inhibition of voltage-gated K+ channel currents by eugenol might be involved in its stimulatory effects [6]. As a wide range of ion channels are already known to be modulated by eugenol, it could have other molecular targets
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