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An Inhibitory Role of Nitric Oxide in the Dynamic Regulation of the Blood-Brain Barrier Function
Authors:Atsushi Yamauchi  Shinya Dohgu  Tsuyoshi Nishioku  Hideki Shuto  Mikihiko Naito  Takashi Tsuruo  Yasufumi Sawada  Yasufumi Kataoka
Institution:(1) Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku Fukuoka, 814-0180, Japan;(2) Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku Tokyo, 113-0032, Japan;(3) Laboratory of Drug Imformatics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 3-14-15 Hongo, Bunkyo-ku Tokyo, 113-0033, Japan;(4) Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku Fukuoka, 814-0180, Japan
Abstract:1. The present study aimed at elucidating the effect of nitric oxide (NO) on blood-brain barrier (BBB) function with mouse brain capillary endothelial (MBEC4) cells. 2. Histamine (20–100 μM) evoked NO production (1.6–7 μM) in MBEC4 cells in a dose-dependent manner. 3. The permeability coefficient of sodium fluorescein for MBEC4 cells and the cellular accumulation of rhodamine 123 in MBEC4 cells were increased dose-dependently by the addition of NO solutions (14 and 28 μM) every 10 min during a 30-min period. 4. The present study demonstrated that NO increased the permeability and inhibited the P-glycoprotein efflux pump of brain capillary endothelial cells, suggesting that NO plays an inhibitory role in the dynamic regulation of the BBB function.
Keywords:nitric oxide  blood-brain barrier (BBB)  permeability  P-glycoprotein  mouse brain endothelial cells
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