Eugenol is widely used as an analgesic in the dental treatment. The underlying mechanisms may involve its modulation of various ion channels. Acid-sensing ion channels (ASICs) are pH sensors and expressed in trigeminal ganglion (TG) neurons. In the present study, we found that eugenol concentration-dependently inhibited ASIC currents in TG neurons with an IC of 98.8 ± 7.4 μM. Eugenol decreased the maximum response to acidic pH and did not alter pH in the concentration-response curve of acidic pH, suggesting a noncompetitive inhibition of ASICs by eugenol. G-proteins were not involved in eugenol-induced inhibition, since pre-application of eugenol also decreased ASIC currents in the presence of the G-protein blocker GDP-β-S. In addition, eugenol also partly inhibited ASIC3 currents in Chinese hamster ovary cells transfected with ASIC3. In conclusion, eugenol partly inhibited ASIC currents in TG neurons in a concentration-dependent, non-competitive and G-protein independent manner. These results suggested that the ASICs could be a molecular target for eugenol in TG neurons, which contributed to its analgesic effect.
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