Effects of Grape Seed Proanthocyanidin on 5-Hydroxytryptamine3 Receptors in NCB-20 Neuroblastoma Cells
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概要
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Proanthocyanidin is a phenolic compound present in plants, that has antioxidant, antinociceptive, anti-emetic, and neuroprotective properties. We investigated the actions of proanthocyanidin from grape seeds on 5-hydroxytryptamine (5-HT)3 receptors in NCB-20 neuroblastoma cells using a whole-cell voltage clamp technique. Co-treatment of proanthocyanidin (0.3—100 μg/ml) and 3 μM 5-HT (near EC50) produced a slight inhibition of 5-HT-induced inward peak current (I5-HT) in NCB-20 cells, but pretreatment with proanthocyanidin for 30 s before application of 5-HT induced a much larger inhibition of I5-HT in an irreversible, concentration- and time-dependent manner (IC50=6.5±0.4 μg/ml, Hill coefficient=2.5±0.1). Proanthocyanidin also produced a concentration-dependent inhibition of currents induced by 30 μM 5-HT, near-maximal concentration (IC50=22.1±0.4 μg/ml, Hill coefficient=2.4±0.1). High concentrations (≧30 μg/ml) of proanthocyanidin caused a concentration-dependent inhibition of the activation and desensitization of currents induced by 30 μM 5-HT. Further studies showed that pretreatment of 20 μg/ml proanthocyanidin caused not only a rightward shift of the dose–response curve for 5-HT (EC50 shift from 2.7±0.4 to 6.2±0.5 μM), but also a decreased Emax (inhibition by 37.5±1.3%). The proanthocyanidin-induced inhibition of 5-HT3 receptors did not show a significant difference within the testing holding potential ranges (−50—+30 mV). These results suggest that proanthocyanidin inhibits 5-HT3 receptor function in NCB-20 cells in a noncompetitive mode, and that this inhibitory effect of proanthocyanidin probably contributes to the pharmacological actions of proanthocyanidin.
- 公益社団法人 日本薬学会の論文
著者
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Kim Ki
Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, Oral Science Res
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Choi Se
Department Of Pharmacology Medical Research Center College Of Medicine The Catholic University Of Ko
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Choi Se
Department Of Obstetrics And Gynecology College Of Medicine The Catholic University Of Korea
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Cho Hyeong
Department Of Pharmacology Medical Research Center College Of Medicine The Catholic University Of Ko
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Kim Ki
Deparment Of Obstetrics & Gynecology College Of Medicine Pusan National University
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SUNG Ki-Wug
Department of Pharmacology, Medical Research Center, College of Medicine, The Catholic University of
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Sung Ki-wug
Department Of Pharmacology Medical Research Center College Of Medicine The Catholic University Of Ko
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Li Qing-Zhong
Department of Pharmacology, The Catholic University of Korea
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Cho Hyeong-Seok
Department of Pharmacology, The Catholic University of Korea
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Jeun Seung-Hyun
Department of Pharmacology, The Catholic University of Korea
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LI Qing-Zhong
Department of Pharmacology, College of Medicine, The Catholic University of Korea
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Sung Ki-Wug
Department of Pharmacology, The Catholic University of Korea
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