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• W4255550688 abstract "The potential of the epithelial cells of the villus-to-crypt surface of the small intestine of the rat to conjugate xenobiotics was studied. The cells were isolated sequentially in the villus-to-crypt gradient and were found to exhibit heterogeneous distribution patterns and inducer-sensitivities of the conjugating enzymes and their cofactors. UDP-glucuronosyltransferase (GT) activities towards 3-hydroxybenzo[a]pyrene (GT1) and 4-hydroxybiphenyl (GT2) were present in all the cells. The mature upper villus cells were rich in both GT1 and GT2 activities, which declined toward the highly replicating undifferentiated crypt cells. The specific enzyme activities were four times lower in crypt cells than in upper villus cells. The presence of GT1 activity always predominated over GT2 activity. 3-Methyl-cholanthrene (3-MC) given orally increased GT1 activity by 2-fold in villus cells and about 6-fold in crypt cells, while phenobarbital sodium salt (PB) also markedly induced GT1 of the crypt region. Unlike GT1, GT2 activity was distinctly induced only by PB in all the cells. Both GT1 and GT2 of crypt cells were highly sensitive to inducers, in comparison to the villus cells. The uridine-5-diphosphoglucuronic acid (UDPGA) content ranged from about 0.07 to 0.2 mM in cells from crypts to villus-tip respectively. 3-MC caused a 3-fold increase in UDPGA content in all the cells; PB, however, did not affect UDPGA. The highest glutathione-S-transferase (GST) activity, however, was towards the substrate 1-chloro-2,4-dinitrobenzene; the basal specific enzyme activity varied from about 0.05 to 0.2 μmol per min per mg protein in cells from crypt to upper villus. The enzyme was induced by both types of inducers, being about 2-fold in villus cells and 3- to 5-fold in crypt cells. In contrast, the GSH content was lower in cells with higher GST activity. The endogenous GSH content ranged from 0.8 mM in the upper-villus cells to 3 mM in the crypt cells. The GSH content, however, was not altered by 3-MC or PB treatment of rats. The results demonstrate that xenobiotic conjugation reactions in intestinal cells are much stronger than monooxygenase reactions. The differential and higher sensitivity of the intestinal cells to inducers appears to provide protection to the intestine against xenobiotics during intestinal “first pass”." @default.
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• W4255550688 date "1988-01-01" @default.
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• W4255550688 title "Localization and characterization of drug-metabolizing enzymes along the villus-crypt surface of the rat small intestine—II" @default.
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• W4255550688 doi "https://doi.org/10.1016/0006-2952(88)90715-0" @default.
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