Volume-activated Cl- secretion and transepithelial vinblastine secretion mediated by P-glycoprotein are not correlated in cultured human T84 intestinal epithelial layers

Abstract

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.