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Biochem Biophys Res Commun. 2000 Jul 14;273(3):1053-7.

Immunochemical identification of UGT isoforms in human small bowel and in caco-2 cell monolayers.

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General Clinical Research Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA.


Previous work had suggested the presence of significant levels of UDP-glucuronosyltransferase 1A1 (UGT1A1) catalytic activity in human small intestinal microsomes, with undetectable to low UGT1A6 and 2B7 activities. To confirm the presence of UGT1A1 isoform in human small bowel, to explore the possible absence of UGT1A6 and 2B7 in the organ, and to examine induced Caco-2 cells as a potential model for human intestinal metabolism, Western blot analysis was performed using specific antibodies to the relevant UGT isoforms. Significant expression of UGT1A1 protein was observed in all samples of human small intestinal microsomes, while UGT1A6 expression was undetectable to faint and UGT2B7 immunoreactivity was faint to detectable. Caco-2 cells treated with typical enzyme-inducing agents resulted in low UGT2B7 expression but failed to mimic the UGT1A1 levels found in human small bowel. Further work needs to be performed to develop a comprehensive in vitro model for human small intestinal first-pass metabolism.

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