Osmotic regulation of sorbitol in the thick ascending limb of Henle's loop.

Organic osmolytes, such as sorbitol, inositol, glycerophosphorylcholine, and betaine, play an important role in the osmoregulation of inner medullary cells of the kidney. The cells of the outer medulla are also exposed to elevated NaCl and urea concentrations during antidiuresis. Therefore, we investigated the mechanisms involved in the regulation of outer medullary organic osmolytes, especially cell sorbitol content of immortalized epithelial cells of the thick ascending limb of Henle's loop (TALH). In the cultured cell model, a 600 mosmol/l medium (osmolarity adjusted by addition of 150 mM NaCl or 300 mM sucrose) increased the intracellular sorbitol content significantly compared with a 300 mosmol/l medium. The accumulation of sorbitol appeared to be due to an increase of aldose reductase activity, which catalyzed sorbitol synthesis. Sorbitol degradation by sorbitol dehydrogenase was not detectable under our experimental conditions. After a sudden decrease of the extracellular osmolarity, the sorbitol permeability of the cellular membrane increased sevenfold within 10 min compared with isosmolar conditions. These results indicate that sorbitol, like inositol, plays an important role in the osmoregulation of TALH cells. Although the short-term regulation involves rapid changes in sorbitol membrane permeability, the longterm adaptation to low osmolarities is regulated by intracellular sorbitol synthesis.