Resveratrol Enhances 5-Hydroxytryptamine Type 3A Receptor-Mediated Ion Currents: The Role of Arginine 222 Residue in Pre-transmembrane Domain I
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概要
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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-HT3A) 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-HT3A receptor channel activity. 5-HT3A 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 H2O as well as on the oocytes injected with 5-HT3A receptor cRNA. In the oocytes injected with 5-HT3A receptor cRNA, co- or pre-treatment of resveratrol with 5-HT potentiated 5-HT-induced inward peak current (I5-HT) with concentration-, reversible, and voltage-independent manners. The EC50 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 I5-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 I5-HT, indicating that resveratrol might interact with pre-TM1 of 5-HT3A receptor. These results indicate that resveratrol might regulate 5-HT3A receptor channel activity via interaction with the N-terminal domain and these results further show that resveratrol-mediated regulation of 5-HT3A receptor channel activity might be one of cellular mechanisms of resveratrol action.
著者
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LEE Byung-Hwan
Department of Physiology, College of Veterinary Medicine, Konkuk University
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CHOI Sun-Hye
Department of Physiology, College of Veterinary Medicine, Konkuk University
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SHIN Tae-Joon
Department of Physiology, College of Veterinary Medicine, Konkuk University
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LEE Sang-Mok
Department of Physiology, College of Veterinary Medicine, Konkuk University
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NAH Seung-Yeol
Department of Physiology, College of Veterinary Medicine, Konkuk University
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Choi Sun
Ginsentology Research Laboratory And Department Of Physiology College Of Veterinary Medicine Konkuk
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Nah Seung-yeol
Department Of Physiology College Of Veterinary Medicine Chonnam National University
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Lee Byung-hwan
Ginsentology Research Laboratory And Department Of Physiology College Of Veterinary Medicine Konkuk
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Hwang Sung-hee
Ginsentology Research Laboratory And Department Of Physiology College Of Veterinary Medicine Konkuk
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Hwang Sung-Hee
Department of Physiology, College of Veterinary Medicine, Konkuk University
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Kang Jiyeon
Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konku
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Hwang Sung-Hee
Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University
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Lee Byung-Hwan
Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University
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Hwang Sung-Hee
Department of Applied Physics, Hanyang University, Ansan, Gyeonggi-do 426-791, Korea
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Nah Seung-Yeol
Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University
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Shin Tae-Joon
Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University
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Choi Sun-Hye
Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University
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Kang Jiyeon
Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University
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Lee Sang-Mok
Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University
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