Hypertonicity-induced accumulation of organic osmolytes in papillary interstitial cells

Background. Medullary cells of the concentrating kidney are exposed to high extracellular solute concentrations. It is well established that epithelia l cells in this kidney region adapt osmotically to hypertonic stress by acc umulating organic osmolytes. Little is known, however, of the adaptive mech anisms of a further medullary cell type, the papillary interstitial cell [r enal papillary fibroblast (RPF)]. We therefore compared the responses of pr imary cultures of RPFs and papillary collecting duct (PCD) cells exposed to hypertonic medium. Methods. In RPFs and PCD cells, organic osmolytes were determined by high-p erformance liquid chromatography; mRNA expression for organic osmolyte tran sporters [Na+/Cl--dependent betaine transporter (BGT), Na+-dependent myo-in ositol transporter (SMIT)], and the sorbitol synthetic and degrading enzyme s [aldose reductase (AR) and sorbitol dehydrogenase (SDH), respectively] wa s determined by Northern blot analysis. Results. Exposure to hypertonic medium (600 mOsm/kg by NaCl addition) cause d intracellular contents of glycerophosphorylcholine, betaine, myo-inositol , and sorbitol, but not free amino acids, to increase significantly in both RPFs and PCD cells. The rise in intracellular contents of these organic os molytes was accompanied by enhanced expression of mRNAs coding for BGT, SMI T, and AR in both RPFs and PCD cells. SDH mRNA abundance, however, was unch anged. Nonradioactive in situ hybridization studies on sections from formal in-fixed and paraffin-embedded, normally concentrating kidneys showed stron g expression of BGT, SMIT, and AR mRNAs in interstitial and collecting duct cells of the papilla, whereas expression of SDH mRNA was much weaker in bo th cell types. Conclusions. These results suggest that both RPFs and PCD cells use similar strategies to adapt osmotically to the high interstitial NaCl concentratio ns characteristic for the inner medulla and papilla of the concentrating ki dney.