Lee Byung-Hwan, Jeong Sang-Min, Lee Jun-Ho, Kim Jong-Hoon, Yoon In-Soo, Lee Joon-Hee, Choi Sun-Hye, Lee Sang-Mok, Chang Choon-Gon, Kim Hyung-Chun, Han YeSun, Paik Hyun-Dong, Kim Yangmee, Nah Seung-Yeol
Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea.
Mol Cells. 2005 Aug 31;20(1):69-73.
The flavonoid, quercetin, is a low molecular weight substance found in apple, tomato and other fruit. Besides its antioxidative effect, quercetin, like other flavonoids, has a wide range of neuropharmacological actions including analgesia, and motility, sleep, anticonvulsant, sedative and anxiolytic effects. In the present study, we investigated its effect on mouse 5-hydroxytryptamine type 3 (5-HT3A) receptor channel activity, which is involved in pain transmission, analgesia, vomiting, and mood disorders. The 5-HT3A receptor was expressed in Xenopus oocytes, and the current was measured with the two-electrode voltage clamp technique. In oocytes injected with 5-HT3A receptor cRNA, quercetin inhibited the 5-HT-induced inward peak current (I(5-HT)) with an IC50 of 64.7 +/- 2.2 microM. Inhibition was competitive and voltage-independent. Point mutations of pre-transmembrane domain 1 (pre-TM1) such as R222T and R222A, but not R222D, R222E and R222K, abolished inhibition, indicating that quercetin interacts with the pre-TM1 of the 5-HT3A receptor.
类黄酮槲皮素是一种存在于苹果、番茄及其他水果中的低分子量物质。除了具有抗氧化作用外，槲皮素与其他类黄酮一样，具有广泛的神经药理学作用，包括镇痛、对运动、睡眠、抗惊厥、镇静及抗焦虑的作用。在本研究中，我们研究了其对小鼠5-羟色胺3型（5-HT3A）受体通道活性的影响，该受体通道与疼痛传递、镇痛、呕吐及情绪障碍有关。5-HT3A受体在非洲爪蟾卵母细胞中表达，采用双电极电压钳技术测量电流。在注射了5-HT3A受体cRNA的卵母细胞中，槲皮素抑制5-羟色胺诱导的内向峰值电流（I(5-HT)），IC50为64.7±2.2微摩尔。抑制作用具有竞争性且与电压无关。跨膜前结构域1（pre-TM1）的点突变，如R222T和R222A，但不是R222D、R222E和R222K，消除了抑制作用，表明槲皮素与5-HT3A受体的pre-TM1相互作用。
