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Type: Journal article
Title: Shed human enterocytes as a tool for the study of expression and function of intestinal drug-metabolizing enzymes and transporters
Author: Glaeser, H.
Drescher, S.
Van der Kuip, H.
Behrens, C.
Geick, A.
Burk, O.
Dent, J.
Somogyi, A.
von Richter, O.
Griese, E.
Eichelbaum, M.
Fromm, M.
Citation: Clinical Pharmacology and Therapeutics, 2002; 71(3):131-140
Publisher: Mosby Inc
Issue Date: 2002
ISSN: 0009-9236
Statement of
Hartmut Glaeser, Siegfried Drescher, Heiko van der Kuip, Christoph Behrens, Anke Geick, Oliver Burk, John Dent, Andrew Somogyi, Oliver von Richter, Ernst-Ulrich Griese, Michel Eichelbaum and Martin F. Fromm
Abstract: Objectives: Intestinal metabolism and transport are now recognized as protective barriers against orally ingested xenobiotics, including drugs. However, in vitro studies of the expression and function of intestinal proteins are hampered by the limited availability of human intestinal tissues. Because enterocytes are constantly shed in large numbers into the gut lumen, this study investigated whether these cells could be collected with a multilumen perfusion catheter and whether they are functionally active. Methods: In healthy volunteers, a 20-cm isolated jejunal segment was generated with the perfusion catheter by inflating 2 balloons with air. Shed cells were characterized by fluorescence-activated cell sorting analysis for leukocyte-specific CD45 and enterocyte-specific villin, as well as for apoptosis. Homogenates of the cells were used for reverse transcriptase polymerase chain reaction and Western blotting. Cytochrome P450 enzyme activity was determined with the calcium channel blocker verapamil as a substrate. Results: On average, 4.83 mg protein and 56.23 million cells were collected from a 20-cm segment during 2 hours. A total of 84.2% of the cells were positive for enterocyte-specific villin, and only 1.6% of the collected cells were positive for CD45. The majority of cells (65.3%) were not in early or late apoptosis or necrosis. In all volunteers, drug-metabolizing enzymes (such as members of the cytochrome P450 family) could be detected as both messenger ribonucleic acid and proteins. Consistent with expression data, formation of verapamil metabolites catalyzed by CYP3A4 and CYP2C was shown. Conclusions: The majority of shed human enterocytes collected with a multilumen perfusion catheter were still functionally active and not apoptotic. Harvesting of spontaneously shed enterocytes provides a new tool for studies on expression and function of intestinal proteins.
Keywords: Enterocytes
Microfilament Proteins
Cytochrome P-450 Enzyme System
Intracellular Signaling Peptides and Proteins
Carrier Proteins
Membrane Proteins
Calcium Channel Blockers
Fluorescent Dyes
Polymorphism, Genetic
Rights: © Mosby
DOI: 10.1067/mcp.2002.121370
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