Volume-activated Cl- secretion and transepithelial vinblastine secretion mediated by P-glycoprotein are not correlated in cultured human T84 intestinal epithelial layers.
The relationship between the P-glycoprotein-mediated vinblastine secretion and cell-swelling activated Cl- secretion (conductance) in intact epithelial layers of human colonic adenocarcinoma T84 cells has been investigated. Whereas vinblastine secretion is effectively inhibited by 100 microM 1,9-dideoxy-forskolin, volume-stimulated Cl- secretion is unaffected. In contrast, 100 microM 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS) inhibited the volume-stimulated Cl- secretion, but was without effect upon transepithelial vinblastine secretion. In addition, it was noted that some epithelial layers failed to express a volume-stimulated Cl- secretion but maintained a normal level of secretory vinblastine flux.
Gastrointestinal Drug Delivery Research Centre, University of Newcastle upon Tyne, Medical School, UK.
G T
GT
McEwan
J
J
Hunter
B H
BH
Hirst
N L
NL
Simmons
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001692:Biological Transport / Q000187:drug effects; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018118:Chloride Channels; D002712:Chlorides; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D005576:Colforsin; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D014747:Vinblastine; C047983:1,9-dideoxyforskolin; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid