Acid-induced stimulation of Na-Pi cotransport in OK cells: molecular characterization and effect of dexamethasone

A. W. Jehle, J. Forgo, J. Biber, E. Lederer, R. Krapf and H. Murer Institute of Physiology, University of Zurich, Switzerland. Alterations in systemic acid/base balance affect renal Pi excretion. In the present study, the effects of an acidic pH on apical Na-dependent Pi (Na-Pi) cotransport were analyzed using OK cells (opossum kidney cell line). Cells were maintained at either pH 7.4 or 7.1 (altered HCO3- concentration at constant PCO2). Incubation in acidic medium led to an increase in Na-Pi cotransport activity, which was characterized by a transient, initial response (2-4 h, 25% increase) followed by a sustained response (24 h, 75% increase). Increased Na-Pi cotransport activity (24 h) was sensitive to inhibition by parathyroid hormone. Actinomycin D did not abolish the acid-induced increases (initial and sustained responses). Cycloheximide abolished the increase in Na-Pi cotransport observed after 24 h. The increase in Na-Pi cotransport (24 h) was prevented by dexamethasone (2 x 10(-6) M). Western blots showed a twofold (3 h) and two- to threefold (24 h) increase in NaPi-4 protein after acid exposure. Cycloheximide prevented the late increase in NaPi-4 protein abundance. Also dexamethasone reduced the increase in specific protein content. In conclusion, the exposure of OK cells to an acidic medium causes a stimulation of the NaPi-4 cotransporter that is prevented by dexamethasone.