Fluoroquinolone (ciprofloxacin) secretion by human intestinal epithelial (Caco-2) cells
Article first published online: 11 FEB 2009
1997 British Pharmacological Society
British Journal of Pharmacology
Volume 121, Issue 8, pages 1567–1578, August 1997
How to Cite
Cavet, M. E., West, M. and Simmons, N. L. (1997), Fluoroquinolone (ciprofloxacin) secretion by human intestinal epithelial (Caco-2) cells. British Journal of Pharmacology, 121: 1567–1578. doi: 10.1038/sj.bjp.0701302
- Issue published online: 11 FEB 2009
- Article first published online: 11 FEB 2009
- (Received December 18, 1996, Revised April 10, 1997, Accepted May 7, 1997)
- Caco-2 cells;
- intestinal secretion;
- 1Human intestinal epithelial Caco-2 cells were used to investigate the mechanistic basis of transepithelial secretion of the fluoroquinolone antibiotic ciprofloxacin.
- 2Net secretion and cellular uptake of ciprofloxacin (at 0.1 mM) were not subject to competitive inhibition by sulphate, thiosulphate, oxalate, succinate and para-amino hippurate, probenecid (10 mM), taurocholate (100 μM) or bromosulphophthalein (100 μM). Similarly tetraethylammonium and N-′methylnicotinamide (10 mM) were without effect.
- 3Net secretion of ciprofloxacin was inhibited by the organic exchange inhibitor 4,4′-diisothiocyanostilbene-2-2′-disulphonic acid (DIDS, 400 μM).
- 4Net secretion of ciprofloxacin was partially inhibited by 100 μM verapamil, whilst net secretion of the P-glycoprotein substrate vinblastine was totally abolished under these conditions. Ciprofloxacin secretion was unaltered after preincubation of cells with two anti-P-glycoprotein antibodies (UIC2 and MRK16), which both significantly reduced secretory vinblastine flux (measured in the same cell batch). Ciprofloxacin (3 mM) failed to inhibit vinblastine net secretion in Caco-2 epithelia, and was not itself secreted by the P-glycoprotein expressing and vinblastine secreting dog kidney cell line, MDCK.
- 5Net secretion and cellular uptake of ciprofloxacin (at 0.1 mM) were not subject to alterations of either cytosolic or medium pH, or dependent on the presence of medium Na+, Cl− or K+ in the bathing media.
- 6The substrate specificity of the ciprofloxacin secretory transport in Caco-2 epithelia is distinct from both the renal organic anion and cation transport. A role for P-glycoprotein in ciprofloxacin secretion may also be excluded. A novel transport mechanism, sensitive to both DIDS and verapamil mediates secretion of ciprofloxacin by human intestinal Caco-2 epithelia.
British Journal of Pharmacology (1997) 121, 1567–1578; doi:10.1038/sj.bjp.0701302