KIDNEY-CELL SURVIVAL IN HIGH TONICITY

The kidney medulla of mammals undergoes large changes in tonicity in p arallel with the tonicity of the final urine that emerges from the kid ney at the tip of the medulla. When the medulla is hypertonic, its cel ls accumulate the compatible osmolytes myo-inositol, betaine, taurine, sorbitol and glycerophosphorylcholine. The mechanisms by which the co mpatible osmolytes are accumulated have been explored extensively in k idney-derived cells in culture. Myo-inositol, betaine and taurine are accumulated by increased activity of specific sodium-coupled transport ers, sorbitol by increased synthesis of aldose reductase that catalyse s the synthesis of sorbitol from glucose. Glycerophosphorylcholine acc umulates primarily because its degradation is reduced in cells in hype rtonic medium. cDNAs for the cotransporters and for aldose reductase h ave been cloned and used to establish that hypertonicity increases the transcription of the genes for the cotransporters for myo-inositol, b etaine and for aldose reductase. The region 5' to the promoter of the gene for the betaine cotransporter and for aldose reductase confer osm otic responsiveness to a heterologous promoter. The 12-bp sequence res ponsible for the transcriptional response to hypertonicity has been id entified in the 5' region of the gene for the betaine cotransporter. ( C) 1991 Elsevier Science Inc.