Metabolic Regulation of Organic Osmolytes in Tubules from Rat Renal Inner and Outer Medulla

Abstract

Glycerophosphorylcholine (GPC), sorbitol and inositol were quantitated in renal tubule suspensions from inner and outer medulla of untreated Sprague-Dawley rats to study the regulation of organic osmolyte concentrations under different metabolic conditions and varying extracellular osmolalities in vitro. Inner medullary tubules prepared in hypertonic saline (550 mosm/kg) contained osmolyte concentrations comparable to those found in the kidney in vivo. Incubation for up to 8 h at 5 mmol/l glucose increased sorbitol in the inner medullary tubules and medium in an osmolality-dependent fashion, whereas GPC and inositol remained constant. At a given glucose concentration the rate of sorbitol formation decreased linearly with increasing tubular sorbitol concentration, which was regulated by an osmolality-dependent export mechanism. Perturbation of tubular mechanisms by inhibition of glycolysis or oxidative phosphorylation did not change the tubular osmolyte content. In contrast to papilla outer medullary tubules contained only inositol. Lactate added as a metabolic substrate to the outer medullary tubules did not change the cellular inositol levels. In outer medullary tubules osmolality changes (320-710 mosm/kg) had no effect on tubular inositol. Addition of furosemide was without effect, when added in vitro. The results indicate that tubular sorbitol formation is regulated by glucose concentration, the level of tubular sorbitol, and an osmolality-dependent export mechanism. In contrast, cellular inositol and GPC levels seem to be independent of acute changes in tubular metabolism.