HETEROGENEOUS DISTRIBUTION OF THE CONJUGATION ACTIVITY OF ACETAMINOPHEN AND p-NITROPHENOL IN ISOLATED RAT LIVER CELLS
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概要
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The uneven distribution of the glucuronidation and sulfation activity of acetaminophen (APAP) and p-nitrophenol (PNP) in liver was studied using centrilobular and periportal regions of isolated rat hepatocytes obtained by Percoll density gradient centrifugation, in a manner similar to that for harmol reported previously. The glucuronidation of APAP and PNP occurred predominantly in the periportal region. Glucuronidation activity of APAP in the centrilobular region was not detected. This finding may reflect the existence of different forms of uridine diphosphate-glucuronyltransferase (UDPGT) for APAP and PNP. The regional difference in K_m values was observed for PNP, but not for harmol as reported in the previous paper. This suggests the existence of multiple forms of UDPGT for PNP as well as the heterogeneous distribution of this enzyme in liver lobules. The sulfation rates of APAP and PNP in the centrilobular region were smaller than those in the periportal region. The regional difference of APAP sulfation was due to different V_<max> values. As shown in the harmol experiment, the predominant distribution of sulfation activity of APAP and PNP in the periportal region agreed with the results in the perfused liver previously reported by other investigators but that of glucuronidation activity was at variance with them.
- 公益社団法人日本薬学会の論文
著者
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HAYASHI Masahiro
Department of Dermatology, Yamagata University School of Medicine
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AWAZU Shoji
Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Science
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MIZUMA Takashi
Department of Biopharmaceutics, Tokyo College of Pharmacy
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Araya Hiroshi
Department of Chemistry, Tokyo Institute of Technology
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HORIE Toshiharu
Departments of Biopharmaceutice, Graduate School of Pharmaceutical Sciences, Chiba University
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AWAZU Shoji
東京薬科大学薬学部 薬物動態制御学教室
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Araya Hiroshi
Department Of Biopharmaceutics Tokyo College Of Pharmacy
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Mizuma Takashi
Department Of Biopharmaceutics Tokyo College Of Pharmacy
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Mizuma Takashi
Department Of Biopharmaceutics And Drug Rational Research Center School Of Pharmacy Tokyo University
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Awazu Shoji
Deparment Of Biopharmaceutics Tokyo College Of Pharmacy
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Hayashi Masahiro
Department Of Biological Production And Enviromental Science Faculty Of Agriculture The University O
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澤山 茂
東京農大 栄養
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Horie Toshiharu
Department Of Biopharmaceutics Graduate School Of Pharmaceutical Sciences Chiba University
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Awazu S
Department Of Biopharmaceutics School Of Pharmacy Tokyo University Of Pharmacy And Life Science
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Mizuma Takashi
Department of Applied Chemistry, Faculty of Engineering, Osaka University
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