Osmotic swelling-provoked release of organic osmolytes in human intestinal epithelial cells.
Human Intestine 407 cells respond to osmotic cell swelling by the activation of Cl(-)- and K(+)-selective ionic channels, as well as by stimulating an organic osmolyte release pathway readily permeable to taurine and phosphocholine. Unlike the activation of volume-regulated anion channels (VRAC), activation of the organic osmolyte release pathway shows a lag time of approximately 30-60 s, and its activity persists for at least 8-12 min. In contrast to VRAC activation, stimulation of organic osmolyte release did not require protein tyrosine phosphorylation, active p21(rho), or phosphatidylinositol 3-kinase activity and was insensitive to Cl(-) channel blockers. Treatment of the cells with putative organic anion transporter inhibitors reduced the release of taurine only partially or was found to be ineffective. The efflux was blocked by a subclass of organic cation transporter (OCT) inhibitors (cyanine-863 and decynium-22) but not by other OCT inhibitors (cimetidine, quinine, and verapamil). Brief treatment of the cells with phorbol esters potentiated the cell swelling-induced taurine efflux, whereas addition of the protein kinase C (PKC) inhibitor GF109203X largely inhibited the response, suggesting that PKC is involved. Increasing the level of intracellular Ca(2+) by using A-23187- or Ca(2+)-mobilizing hormones, however, did not affect the magnitude of the response. Taken together, the results indicate that the hypotonicity-induced efflux of organic osmolytes is independent of VRAC and involves a PKC-dependent step.
|Keywords||Anion Transport Proteins/drug effects/metabolism, Biological Transport, Active/drug effects/physiology, Carrier Proteins/drug effects/metabolism, Cell Line, Cell Membrane Permeability/drug effects/*physiology, Cell Size/drug effects/physiology, Chloride Channels/drug effects/metabolism, Electrolytes/*metabolism, Enzyme Inhibitors/pharmacology, Epithelial Cells/cytology/drug effects/*metabolism, Humans, Intestines/cytology/drug effects/*metabolism, Ion Channels/drug effects/*metabolism, Osmolar Concentration, Osmotic Pressure/drug effects, Protein Kinase C/antagonists & inhibitors/metabolism, Reaction Time/drug effects/physiology, Research Support, Non-U.S. Gov't, Taurine/metabolism, Water-Electrolyte Balance/drug effects/*physiology|
|Persistent URL||dx.doi.org/10.1152/ajpcell.00468.2003, hdl.handle.net/1765/13306|
Tomassen, S.F.B., Fekkes, D., de Jonge, H.R., & Tilly, B.C.. (2004). Osmotic swelling-provoked release of organic osmolytes in human intestinal epithelial cells.. American Journal of Physiology: Cell Physiology, 286(6 55-6), 1417–1422. doi:10.1152/ajpcell.00468.2003