Resveratrol Inhibits GABA(C) ρ Receptor-Mediated Ion Currents Expressed in Xenopus Oocytes

Resveratrol is a phytoalexin found in grapes, red wine, and berries. Resveratrol has been known to have many beneficial health effects, such as anti-cancer, neuroprotective, anti-inflammatory, and life-prolonging effects. However, relatively little is known about the effects of resveratrol on the regulation of ligand-gated ion channels. We have previously reported that resveratrol regulates subsets of homomeric ligand-gated ion channels such as those of 5-HT(3A) receptors. The γ-aminobutyric acid(C) (GABA(C)) receptor is mainly expressed in retinal bipolar cells and plays an important role in visual processing. In the present study, we examined the effects of resveratrol on the channel activity of homomeric GABA(C) receptor expressed in Xenopus oocytes injected with cRNA encoding human GABA(C) ρ subunits. Our data show that the application of GABA elicits an inward peak current (I(GABA)) in oocytes that express the GABA(C) receptor. Resveratrol treatment had no effect on oocytes injected with H(2)O or with GABA(C) receptor cRNA. Co-treatment with resveratrol and GABA inhibited I(GABA) in oocytes with GABA(C) receptors. The inhibition of I(GABA) by resveratrol was in a reversible and concentration-dependent manner. The IC(50) of resveratrol was 28.9±2.8 µM in oocytes expressing GABA(C) receptor. The inhibition of I(GABA) by resveratrol was in voltage-independent and non-competitive manner. These results indicate that resveratrol might regulate GABA(C) receptor expression and that this regulation might be one of the pharmacological actions of resveratrol on the nervous system.