Rapid stimulation of Na+/H+ exchange by 1,25-dihydroxyvitamin D3; interaction with parathyroid-hormone-dependent...

We have examined the rapid effect of 1,25-dihydroxyvitamin-D3 [1,25(OH)2D3] on apical Na+/H+ exchange activity in opossum kidney (OK) cells and in MCT cells (a culture of simian-virus-40-immortalized mouse cortical tubule cells) grown on filter support. Addition of 1,25(OH)2D3 (10 nM) for 1 min increased apical Na+/H+ exchange activity [recovery from an acid load; measured by 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein] in OK cells (by 56%) and in MCT cells (by 36%). The cellular mechanisms involved in 1,25(OH)2D3-dependent stimulation of Na+/H+ exchange were analysed in OK cells; stimulation of Na+/H+ exchange by 1,25(OH)2D3 was not prevented by actinomycin D. Applying parathyroid hormone (PTH) reduced Na+/H+ exchange activity in OK cells (by 34% at 10 nM, 5 min); 1,25(OH)2D3 "reversed" PTH-induced inhibition, either when PTH was added prior to 1,25(OH)2D3 or when the two agonists were applied together. 1,25(OH)2D3 had no effect on basal OK cell cAMP content or on [Ca2+]i (fura-2). 1,25(OH)2D3 attenuated PTH-induced cAMP accumulation and had no effect on the PTH-dependent increase in [Ca2+]i. These data suggest a regulatory control (stimulation) of proximal tubular brush-border Na+/H+ exchange by 1,25(OH)2D3. This effect is non-genomic and might in part be explained by a release from cAMP-dependent control of transport activity.