The Uptake Mechanism of Gallium-67 into Hepatocytes Treated with Carbon Tetrachloride(Biochemistry)

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概要

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• We have recently reported that transferrin (Tf)-unbound gallium-67 (^<67>Ga) may be taken up into the liver of carbon tetrachloride (CCl_4)-treated rats. In the present study, we attempted to clarify detailed mechanism of Tf-unbound ^<67>Ga uptake by hepatocytes treated with CCl_4 using in vitro experimental system. Hepatotoxic damages by CCl_4 are mostly attributed to radical formed by an action of cytochrome P450. P450 isozymes have a higher expression in the perivenous hepatocytes (PVH) more than periportal hepatocytes (PPH). Therefore, we thought that the uptake of ^<67>Ga which had been used for the detection of liver damage might have a zonal difference. The results of ALT activities showed that the CCl_4 exposure for 4h strongly impaired PVH more than PPH. The uptake of ^<67>Ga by PVH treated with CCl_4 was also higher than that by PPH. Moreover, the uptake of ^<45>Ca by PVH was higher than that by PPH. In order to investigate whether ^<67>Ga passed through calcium channel of hepatocytes, we made use of calcium channel blocker and activator. The Ca^<2+>-channel blocker, verapamil, significantly decreased the uptakes of ^<45>Ca and ^<67>Ga by PPH and PVH pretreated with CCl_4. The addition of the Ca^<2+>-channel activator, Bay K8644, significantly increased the uptake both of ^<45>Ca and ^<67>Ga by PPH pretreated with CCl_4. In the present study, it was demonstrated that the uptake of Tf-unbound ^<67>Ga preferentially occurred in CCl_4-damaged PVH and ^<67>Ga was taken up into the hepatocytes in part through calcium channel.

• 公益社団法人日本薬学会の論文
• 2007-02-01

著者

• OHTAKE Yosuke

  Department of Radiopharmacology, Tohoku Pharmaceutical University

• OHKUBO Yasuhito

  Department of Radiopharmacology, Tohoku Pharmaceutical University

• Ohtake Yosuke

  Dep. Of Radiopharmacology Tohoku Pharmaceutical Univ.

• ABE Shinya

  Department of Radiopharmacy, Tohoku Pharmaceutical University

• Satoh Satoko

  Department Of Radiopharmacy Tohoku Pharmaceutical University

• Ohuchi Yukie

  Department Of Radiopharmacy Tohoku Pharmaceutical University

• Ohkubo Yasuhito

  Department Of Radiopharmacology Tohoku Pharmaceutical University

• Abe Shinya

  Department Of Radiopharmacy Tohoku Pharmaceutical University

• 大窪 芳子

  Department Of Radiopharmacy Tohoku Pharmaceutical University

• Ohtake Yosuke

  Department Of Radiopharmacology Tohoku Pharmaceutical University

• Suyama Satoko

  Department Of Radiopharmacy Tohoku Pharmaceutical University

• CHIBA Seiko

  Department of Radiopharmacy, Tohoku Pharmaceutical University

• NAKAO Hajime

  Department of Radiopharmacy, Tohoku Pharmaceutical University

• Chiba Seiko

  Department Of Radiopharmacy Tohoku Pharmaceutical University

• Nakao Hajime

  Department Of Radiopharmacy Tohoku Pharmaceutical University

• Nakao Hajime

  Department Of Physics Kwansei Gakuin University

• Abe Shinya

  Department Of Cardiology Tobu Chiiki Hospital Tokyo Metropolitan Health And Medical Treatment Corpor

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