Regulation of rat ileal NHE3 by 1,25 (OH)₂-vitamin D₃

We have previously demonstrated a modulation of Na⁺/H⁺ exchange (NHE) activity by vitamin D₃ in the rat ileum and Caco-2 cells. However, the molecular mechanism(s) of action of vitamin D₃ on NHE are still not understood. The current studies were undertaken to understand the regulation of individual NHE isoforms on mRNA levels in two distinct models of vitamin D₃ deficiency. Acute D₃ deficiency was induced secondary to streptozotocin-induced diabetes mellitus, while chronic D₃ deficiency was induced by feeding a D₃-deficient diet in an environment devoid of fluorescent light. Vitamin D₃ deficiency in both models increased the initial rates of rat ileal brush-border membrane (BBM) Na⁺/H⁺ exchange by 2.5-fold compared to D-repleted controls. In parallel to the increased exchanger activity, NHE3 mRNA abundance was increased about twofold in both acute and chronic D deficiency compared to control. There was no change in NHE1 or NHE2 abundance in vitamin D₃-deficient rat ileum. These findings indicate that vitamin D₃ regulates Na⁺/H⁺ exchange activity in rat ileum by influencing the mRNA levels of NHE3, the predominant luminal membrane isoform involved in vectorial Na⁺ transport.