Resveratrol Inhibits Glycine Receptor-Mediated Ion Currents

Abstract

Resveratrol is found in grapes, red wine, and berries. Resveratrol has been known to have many beneficial health effects, such as anti-cancer, neuroprotective, anti-nociceptive, and life-prolonging effects. However, the single cellular mechanisms by which resveratrol acts are relatively unknown, especially in terms of possible regulation of receptors involved in synaptic transmission. The glycine receptor is an inhibitory ligand-gated ion channel involved in fast synaptic transmission in spinal cord. In the present study, we investigated the effect of resveratrol on human glycine receptor channel activity. Glycine α1 receptors were expressed in Xenopus oocytes and glycine receptor channel activity was measured using a two-electrode voltage clamp technique. Treatment with resveratrol alone had no effect on oocytes injected with H 2 O or on oocytes injected with glycine α1 receptor cRNA. In the oocytes injected with glycine α1 receptor cRNA, co-or pretreatment of resveratrol with glycine inhibited the glycine-induced inward peak current (I Gly ) in a reversible manner. The inhibitory effect of resveratrol on I Gly was also concentration dependent, voltage independent, and non-competitive. These results indicate that resveratrol regulates glycine receptor channel activity and that resveratrol-mediated regulation of glycine receptor channel activity is one of several cellular action mechanisms of resveratrol for pain regulation.Key words resveratrol; glycine; glycine receptor; ligand-gated ion channel; Xenopus oocyte Resveratrol is a phytoalexin found in grapes, red wine, and other berries (Fig. 1A) and is also produced as an anti-fungal chemical by plants.1) The concentration of resveratrol in red wine is as high as 0.2-5.8 mg/L.2) Resveratrol exhibits diverse physiological and pharmacological activities, such as anti-cancer, chemopreventive, antiviral, cardio-protective, anti-aging, anti-nociceptive, and life-prolonging effects.2-4) Resveratrol exhibits beneficial effects on the nervous system. It attenuates neurodegenerative disorders such as Alzheimer's disease.5) It also attenuates neuronal cell death from in vitro or in vivo brain hypoxia or ischemic conditions. 6,7) Although accumulating evidence indicates that resveratrol has diverse beneficial properties, including protective effects on the nervous system, relatively little is known about its cellular action, especially with respect to possible regulation of the receptors involved in synaptic transmission.The glycine receptor belongs to the superfamily of ligandgated ion channel receptors that are structurally similar to nicotinic acetylcholine, 5-HT 3 , and γ-aminobutyric acid A (GABA A ) receptors. 8,9) Glycine receptors are dominantly expressed in the spinal cord.10) The physiological roles of glycine receptors in these regions mediate post-synaptic inhibition for reflex responses, voluntary motor control, and the processing of sensory signals, 10) because the glycine receptor forms a chloride-permeable and -selective transmembrane channel. Glycine recep...

Modern opportunities and prospects for preserving woman’s health

“…Ресвератрол -природний фітоалексин (стильбен, поліфенол), що у природних умовах продукується певними рослинами та існує в двох ізомерних формах: транс-і цисресвератрол (з перетворенням трансізомеру у цис-форму при ультрафіолетовому опроміненні); при цьому транс-ресвератрол є основною біологічно активною формою [41,42].…”

Modulators of the Inhibitory Glycine Receptor

“…It is known to have many beneficial effects, such as anticancer, neuroprotective, neuroregenerative, and antinociceptive activities. Resveratrol is a noncompetitive inhibitor of α1 GlyRs expressed in Xenopus laevis oocytes …”

“…Resveratrol is a noncompetitive inhibitor of α1 GlyRs expressed in Xenopus laevis oocytes. 71 Neuroactive steroids are both positive and negative modulators of GABA A Rs and GlyRs. 72 The steroids pregnenolone sulfate and dehydroepiandrosterone sulfate as well as alphaxalone and its 3β-epimer betaxalone inhibited GlyR responses in cultured rat spinal cord neurons with IC 50 values ranging from 16 to 208 μM; no potentiation was observed.…”

Change the channel: CysLoop receptor antagonists from nature

“…Polyphenol resveratrol occurs in grapes, red wine, and berries, and exhibits diverse physiological and pharmacological properties including antioxidant, anticancer, antiviral and anti‐nociceptive activity. Resveratrol non‐competitively antagonizes chloride currents of human α1 GlyRs expressed in Xenopus oocytes 73 . Moreover, resveratrol also showed insecticidal activities against multiple pests, such as the oriental armyworm (mortality 50%/600 mg L −1 ), cotton bollworm (mortality 25%/600 mg L −1 ), corn borer (mortality 35%/600 mg L −1 ), adult mite (mortality 70%/600 mg L −1 ), and mosquito (mortality 30%/10 μg mL −1 ) 74 .…”