Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea.
Biol Pharm Bull. 2011;34(4):523-7. doi: 10.1248/bpb.34.523.
Resveratrol, which is found in grapes, red wine, and berries, has many beneficial health effects, such as anti-cancer, neuro-protective, anti-inflammatory, and life-prolonging effects. However, the cellular mechanisms by which resveratrol acts are relatively unknown, especially in terms of possible regulation of receptors involved in synaptic transmission. 5-Hydroxytryptamine type 3A (5-HT(3A)) receptor is one of several ligand-gated ion channels involved in fast synaptic transmission. In the present study, we investigated the effect of resveratrol on mouse 5-HT(3A) receptor channel activity. 5-HT(3A) receptor was expressed in Xenopus oocytes, and the current was measured using a two-electrode voltage clamp technique. Treatment of resveratrol itself had no effect on the oocytes injected with H(2)O as well as on the oocytes injected with 5-HT(3A) receptor cRNA. In the oocytes injected with 5-HT(3A) receptor cRNA, co- or pre-treatment of resveratrol with 5-HT potentiated 5-HT-induced inward peak current (I(5-HT)) with concentration-, reversible, and voltage-independent manners. The EC(50) of resveratrol was 28.0±2.4 µM. The presence of resveratrol caused a leftward shift of 5-HT concentration-response curve. Protein kinase C (PKC) activator or inhibitor had no effect on resveratrol action on I(5-HT). Site-directed mutations of pre-transmembrane domain 1 (pre-TM1) such as R222A, R222D, R222E, R222K, and R222T abolished or attenuated resveratrol-induced enhancement of I(5-HT), indicating that resveratrol might interact with pre-TM1 of 5-HT(3A) receptor. These results indicate that resveratrol might regulate 5-HT(3A) receptor channel activity via interaction with the N-terminal domain and these results further show that resveratrol-mediated regulation of 5-HT(3A) receptor channel activity might be one of cellular mechanisms of resveratrol action.
白藜芦醇存在于葡萄、红酒和浆果中，具有许多有益的健康作用，如抗癌、神经保护、抗炎和延长寿命。然而，白藜芦醇作用的细胞机制相对未知，特别是在可能调节涉及突触传递的受体方面。5-羟色胺 3A（5-HT3A）受体是参与快速突触传递的几种配体门控离子通道之一。在本研究中，我们研究了白藜芦醇对小鼠 5-HT3A 受体通道活性的影响。5-HT3A 受体在非洲爪蟾卵母细胞中表达，并使用双电极电压钳技术测量电流。白藜芦醇本身处理对注射 H2O 的卵母细胞以及注射 5-HT3A 受体 cRNA 的卵母细胞没有影响。在注射 5-HT3A 受体 cRNA 的卵母细胞中，白藜芦醇与 5-HT 共同或预先处理以浓度、可逆和电压独立的方式增强 5-HT 诱导的内向峰值电流（I5-HT）。白藜芦醇的 EC50 为 28.0±2.4 μM。白藜芦醇的存在导致 5-HT 浓度-反应曲线向左移位。蛋白激酶 C（PKC）激活剂或抑制剂对 I5-HT 上的白藜芦醇作用没有影响。跨膜结构域 1 前（pre-TM1）的定点突变，如 R222A、R222D、R222E、R222K 和 R222T，消除或减弱了白藜芦醇诱导的 I5-HT 增强，表明白藜芦醇可能与 5-HT3A 受体的 pre-TM1 相互作用。这些结果表明，白藜芦醇可能通过与 N 端结构域相互作用来调节 5-HT3A 受体通道活性，这些结果进一步表明，白藜芦醇介导的 5-HT3A 受体通道活性的调节可能是白藜芦醇作用的细胞机制之一。
