6533b853fe1ef96bd12ac293

RESEARCH PRODUCT

THE DISTRIBUTION OF UDP-GLUCURONOSYLTRANSFERASES IN RAT-LIVER PARENCHYMAL AND NONPARENCHYMAL CELLS

Franz OeschBrian BurchellMichael ArandPablo SteinbergMichael W.h. Coughtrie

subject

MaleAroclorsCell type1303 BiochemistryKupffer CellsLiver cytologyBilirubinBlotting WesternGlucuronidation10050 Institute of Pharmacology and Toxicology610 Medicine & healthCell SeparationBiologyBiochemistryIsozymechemistry.chemical_compoundSulfationmedicineAnimalsEndotheliumGlucuronosyltransferasePharmacologyKupffer cellRats Inbred StrainsChlorodiphenyl (54% Chlorine)ArylsulfotransferaseMolecular biologyRatsIsoenzymesEndothelial stem cellmedicine.anatomical_structure3004 PharmacologyLiverchemistryBiochemistry570 Life sciences; biology

description

Activities for the glucuronidation of 1-naphthol, morphine and bilirubin as well as for the sulfation of 2-naphthol have been determined in homogenates of parenchymal, Kupffer and endothelial cells isolated from livers of untreated and Aroclor 1254-pretreated rats. In addition, Western blot analyses using different polyclonal antibodies against UDP-glucuronosyltransferases (UDP-GTs) were performed with similar preparations. All enzymes under investigation were expressed at high levels in liver parenchymal cells. The constitutive expression and inducibility of UDP-GT isozyme(s) for 1-naphthol glucuronidation was also clearly demonstrated in Kupffer and endothelial cells. Furthermore, the presence of other UDP-GT isozymes was detected in preparations from these cells. No significant sulfation of 2-naphthol was detectable in Kupffer and endothelial cell homogenates. While the glucuronidation of 1-naphthol and morphine was significantly induced in all cell types by Aroclor 1254-pretreatment of the animals, the glucuronidation of bilirubin and the sulfation of 2-naphthol remained unchanged. Since the specific activity of conjugation reactions is much lower in liver nonparenchymal cells than in liver parenchymal cells, and nonparenchymal cells contribute only about 6% to the total liver protein, protection of the cells themselves rather than contribution to the overall metabolism of xenobiotics seems to be the significant role of these xenobiotic-metabolizing enzymes in the sinusoidal lining cells.

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