Effects of tributyltin on barrier functions in human intestinal Caco-2 cells.
The effect of tributyltin (TBT) on human intestinal epithelial cell functions was investigated by using human intestinal Caco-2 cell monolayers. We paid particular attention to the effect of TBT on two barrier functions: the tight junction as a physical barrier and MDR1/P-glycoprotein as a biological barrier. A loss of monolayer integrity was apparent from the TBT treatment and the paracellular permeability was increased by TBT. On the other hand, the activity of P-glycoprotein, which was examined by measuring the accumulation of Rhodamine-123 and daunomycin, was increased by prolonged TBT treatment in a concentration-dependent manner (1-100 nM). Furthermore, it was clarified by Western and Northern blots that this increase was accompanied by the increased expression of MDR1 mRNA and protein. The activation of a multidrug resistance transporter P-glycoprotein by TBT would cause a disorder of the human intestines by changing the drug pharmacokinetics.
Tsukazaki
Masashi
M
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Satsu
Hideo
H
Mori
Akira
A
Sugita-Konishi
Yoshiko
Y
Shimizu
Makoto
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000378:metabolism*; D008841:Actin Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D000469:Alkaline Phosphatase / Q000378:metabolism; D018826:CD13 Antigens / Q000378:metabolism; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D017097:Electric Impedance; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D007546:Isoquinolines / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000096:biosynthesis; D020112:Rhodamine 123 / Q000493:pharmacokinetics; D019108:Tight Junctions / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D014220:Trialkyltin Compounds / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007546:Isoquinolines; D012333:RNA, Messenger; D014220:Trialkyltin Compounds; D020112:Rhodamine 123; C011559:tributyltin; C017475:lucifer yellow; D000469:Alkaline Phosphatase; D018826:CD13 Antigens; D003630:Daunorubicin