Response of renal medullary cells to osmotic stress

In antidiuresis renal medullary cells are exposed to high NaCl and urea concentrations. Long-term adaptation of renal medullary cells to high extracellular NaCl concentrations is accomplished by intracellular accumulation of organic osmolytes. The underlying mechanisms include enhanced uptake from the extracellular space (betaine, myo-inositol and amino acids), increased intracellular production [sorbitol and glycerophosphorylcholine (GPC)] and reduced intracellular degradation (GPC). Apart from osmotically balancing the high extracellular NaCl concentration, betaine and GPC also contribute to protecting medullary cells against the adverse effects of high urea concentrations. A similar function has been demonstrated for HSP70, which is expressed abundantly in the inner medulla. The functional significance of osmolyte accumulation and HSP70 expression for medullary cells is highlighted by observations showing that inappropriately low rates of intracellular osmolyte accumulation or HSP70 expression are associated with an increased incidence of apoptotic cell death.