SITE-SPECIFIC REGULATION OF ORGANIC OSMOLYTES ALONG THE RAT NEPHRON

The regulation of organic osmolytes was investigated in acute furosemi de and chronic lithium diuresis along the nephron and in urinary bladd er of rats. Sorbitol, myo-inositol, glycerophosphorylcholine, and beta ine were measured enzymatically or by high-performance liquid chromato graphy in homogenates and bioluminometrically in microdissecaed tubule s. In untreated rats, all osmolytes except myo-inositol increased alon g the corticopapillary axis. An efflux of all osmolytes (- 50%) was ob served in homogenates of outer and inner medulla after acute furosemid e diuresis (15 min, urinary osmolality = 329 mosmol/kgH(2)O) and for b oth polyols in microdissected tubules (30 min). In urinary bladder, on ly low concentrations of myoinositol were found not to be affected by furosemide treatment. Chronic lithium treatment(7 days; urinary osmola lity = 385 mosmol/kgH(2)O) decreased inner medullary but not outer med ullary osmolyte concentrations. The results confirm a site-specific or ganic osmolyte pattern along the rat nephron, which is rapidly changed in a segment-specific way by different mechanisms of diuresis. The bl adder epithelium does not accumulate organic osmolytes because no ''os motic gap'' exists across the basolateral membrane. The osmotic differ ence across the apical membrane is maintained by the apical tightness of these cells.