Regulation of 86Rb+ ion transport across polarized human colonocytes by bis-phenolic compounds.
1. Phenolphthalein, a well-known laxative, stimulates the secretion of Na+ and Cl- ions and accompanying water into the intestinal tract. Measurement of 86Rb+ efflux from several, but not all, cell types indicates that phenolphthalein also results in release of cellular K+ ions. 2. In the present study, the transport of 86Rb+ across human colonocyte cells (T84) cultured on trans-well inserts was examined. The T84 cells were cultured until they developed tight junctions and a high trans-epithelial resistance. 3. Results show that phenolphthalein applied to the apical, but not the basolateral, surface of cells causes the release of 86Rb+ from the apical surface. Basolateral treatment of cells with phenolphthalein had no effect on the release of 86Rb+. 4. Simultaneously with the increased 86Rb+ efflux, indirect evidence of enhanced Na+/K+-ATPase activity was also observed. 5. Although ouabain inhibited the increased Na+ pump activity, it did not affect apical 86Rb+ release. 6. As evidenced by near steady state 86Rb+ uptake data, the increased Na+/K+-ATPase activity was insufficient to restore intracellular concentrations of K+ in the presence of phenolphthalein. 7. 4,4(9-Fluorenylidene)diphenol, a homologue of phenolphthalein, had a similar effect on 86Rb+ transport by T84 cells. 8. These results indicate a primary stimulation of 86Rb+ efflux from the apical surface of polarized T84 cells by apically applied bis-phenolic compounds. 9. A secondary stimulation of the basolateral Na+/K+-ATPase is thought to result from intracellular Na+ increase, as documented in several other cell types exposed to bis-phenolic compounds, although not directly measured in these experiments. 10. The results also indicate that bis-phenolic compounds interact specifically with some apical but not basolateral membrane structures in regulating 86Rb+ efflux from polarized T84 cells.
Mason
Robert W
RW
Departments of Pediatrics and Biomedical Research, Nemours Children's Clinic, Alfred I duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE 19803, USA. rmason@nemours.org
Simpson-Small
Tiffani
T
Hopp
Laszlo
L
D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D010042:Ouabain / Q000494:pharmacology; D020113:Phenolphthalein / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology*; D012414:Rubidium Radioisotopes / Q000493:pharmacokinetics*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism
D010636:Phenols; D012414:Rubidium Radioisotopes; D010042:Ouabain; D020113:Phenolphthalein; D000254:Sodium-Potassium-Exchanging ATPase