Evaluation of Blood-Brain Barrier Transporters by Co-culture of Brain Capillary Endothelial Cells with Astrocytes

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  To investigate the transport function of the blood-brain barrier (BBB), we employed an <i>in vitro</i> model of the BBB, consisting of a co-culture of porcine brain capillary endothelial cells (BCECs) with rat astrocytes. Porcine BCECs were cultured on a filter insert with rat astrocytes on the underlying plastic well. Rat astrocytes induced characteristic BBB properties of porcine BCECs, such as γ-glutamyl-transpeptidase activity and intercellular adhesion of porcine BCECs. Next, the transport properties of P-glycoprotein (P-gp) substrate and several anionic compounds across the co-cultured porcine BCECs were characterized. Expression of P-gp was detected by immunocytochemistry, and efflux-directed transport of the P-gp substrate [<sup>3</sup>H]daunomycin was observed. Luminal-to-abluminal transport of the monocarboxylic acid transporter 1 (MCT1) substrate [<sup>14</sup>C]benzoic acid was saturable, and the <i>K</i><sub>m</sub> value (3.05 mM) was similar to that for brain uptake observed <i>in vivo</i>. Abluminal-to-luminal transport of [<sup>14</sup>C]benzoic acid was also saturable, indicating that the monocarboxylic acid transporter of the BBB contributes to the efflux from the brain as well as to blood-to-brain influx. Abluminal-to-luminal transport of organic anions, [<sup>3</sup>H]dehydroepiandrosterone sulfate, [<sup>3</sup>H]estrone sulfate and [<sup>3</sup>H]estradiol 17β-D-glucuronide was significantly higher than the corresponding luminal-to-abluminal transport. These results demonstrate the presence of multiple efflux transport pathways in this <i>in vitro</i> model.<br>

収録刊行物

  • Drug metabolism and pharmacokinetics

    Drug metabolism and pharmacokinetics 17(1), 34-41, 2002-03-29

    The Japanese Society for the Study of Xenobiotics

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各種コード

  • NII論文ID(NAID)
    10008197998
  • NII書誌ID(NCID)
    AA1162652X
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    09161139
  • データ提供元
    CJP書誌  CJP引用  J-STAGE 
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