AJP - Renal Physiology, Vol 270, Issue 2 275-F282, Copyright © 1996 by American Physiological Society
Osmotic regulation of sorbitol in the thick ascending limb of Henle's loop
A. Eckstein and R. W. Grunewald
Sektion Nephrologie, Universitatsklinik Ulm, Germany.
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.
