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Influence of low dietary histamine on the seizure development of chemical kindling induced by pentylenetetrazol in rats

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Acta Pharmacologica Sinica 2005年第4期26卷 423-427页

作者： eiko sakurai Yoshinobu KISO Kazuhiko YANAI Department of Pharmacology Tohoku University School of Medicine Sendai 980-8575 Japan Department of Pharmacology School of Medicine Zhejiang University Hangzhou 310031 China Department of Pharmacologv School of Medicine Zhejiang University Hangzhou 310031 China Department of Pharmacology Tohoku University School of Medicine Sendai 980-8575 Japan

Aim:To determine the role of dietary low histamine on the seizure development ofpentylenetetrazol (PTZ)-induced kindling in ***:After 14 d of feedingon a low histamine diet (LH,containing 0.145 μmol/g of histamine),the rats werechemically kindled by repeated intraperitoneal injection of a subconvulsant doseof PTZ (35 mg/kg) once every 48 h,and seizure activity of kindling was recordedfor 30 *** in brain samples was analyzed using a high performanceliquid chromatography system with a fluorescence ***:The LH diet induced an increase in seizure response (seizure susceptibility) to thefirst trial of PTZ,and resulted in facilitation of subsequent PTZ kindling process(seizure development).The histamine levels in the cortex,hippocampus,andhypothalamus of LH-treated rats decreased significantly and these changes cor-related well with seizure behavior (r=0.875,0.651,and 0.796,respectively).In addition,chronic kindled seizures resulted in a significant increase of the histamine contentin the cortex and hypothalamus in the LH-fed ***:These find-ings indicate that the histamine in daily food could influence the brain histaminer-gic function,and play an important role in regulating seizure susceptibility.

关键词： seizures pentylenetetrazol brain histamine diet

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Flavin-Containing Monooxygenase (FMO) Protein Expression and Its Activity in Rat Brain Microvascular Endothelial Cells

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Pharmacology & Pharmacy 2013年第1期4卷 1-6页

作者： Eiichi sakurai Yukari Ueda Yukari Mori Yasuhumi Shinmyouzu eiko sakurai Department of Pharmaceutics Faculty of Pharmaceutical Sciences Tokushima Bunri University Tokushima Japan Faculty of Pharmacy Iwaki Meisei University Fukushima Japan

The aim of this study was to examine whether flavin-containing monooxygenase (FMO) protein was expressed in cultured rat brain microvascular endothelial cells (BMECs), which constitute the blood-brain barrier (BBB), and whether N-oxide from the tertiary amine, d-chlorpheniramine, was formed by FMO in rat BMECs. BMECs were isolated and cultured from the brains of three-week-old male Wistar rats. The expression of FMO1, FMO2 and FMO5 proteins was confirmed in rat BMECs by western blotting analysis using polyclonal anti-FMO antibodies, but FMO3 and FMO4 proteins were not found in the rat BBB. Moreover, N-oxide of d-chlorpheniramine was formed in rat BMECs. The intrinsic clearance value for N-oxidation at pH 8.4 was higher than that at pH 7.4. Inhibition of N-oxide formation by methimazole was found to be the best model of competitive inhibition yielding an apparent Ki value of 0.53 μmol/L, suggesting that N-oxidation was catalyzed by FMOs in rat BMECs. Although FMO activity in rat BMECs was lower than that in SD rat normal hepatocytes (rtNHeps), we suggest that rat BMECs enzymes can convert substrates of exogenous origin for detoxification, indicating that BMECs are an important barrier for metabolic products besides hepatic cells.

关键词： Rat Microvascular Endothelial Cells Flavin-Containing Monooxygenase (FMO) FMO Protein Expression FMO Activity BBB

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Claudin-1 Leads to Strong Formation of Tight Junction in Cultured Mouse Lung Microvascular Endothelial Cells

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Pharmacology & Pharmacy 2016年第3期7卷 133-139页

作者： Yukari Ueda Yasuhumi Shinmyouzu Hikaru Nakayama Tadatoshi Tanino eiko sakurai Eiichi sakurai Department of Pharmaceutics Faculty of Pharmaceutical Sciences Tokushima Bunri University Tokushima Japan Faculty of Pharmacy Iwaki Meisei University Fukushima Japan

We aimed to examine paracellular barrier function in cultured mouse lung microvascular endothelial cells (LMECs). The transcellular resistance of LMEC monolayers yielded an electrical resistance of approximately 19 Ω × cm2 at days 6 - 7 in culture when the cells reached confluence, and paracellular permeable clearance of sodium fluorescein was the lowest on day 6 in culture, suggesting the formation of tight junctions (TJs) in cultured LMECs. Moreover, the expression of TJ-associated proteins, occludin, claudin-1 and -4 and zonula occludents 1 (ZO-1) was detected in LMECs at day 6 in culture. However, mRNAs of occludin, claudin-1 and -4 and ZO-1 were already expressed on day 1 after culture, and large variations were absent in the mRNA levels of occludin, claudin-4 and ZO-1 between days 1 and 7 in culture, when the level of each mRNA on day 1 in culture was used as a basal level. However, the claudin-1 mRNA level gradually increased up to approximately 7-fold on day 7 in culture over the basal level. These results indicate that the drastic increase in the mRNA expression level of claudin-1 leads to the strong formation of TJs.

关键词： Mouse Lung Microvascular Endothelial Cells Paracellular Permeability Tight Junction Occludin Claudins Zonula Occludents

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