Site-specific regulation of organic osmolytes along the rat nephron

The regulation of organic osmolytes was investigated in acute furosemide and chronic lithium diuresis along the nephron and in urinary bladder of rats. Sorbitol, myo-inositol, glycerophosphorylcholine, and betaine were measured enzymatically or by high performance liquid chromatography in homogenates and bioluminometrically in microdissected tubules. In untreated rats, all osmolytes except myo-inositol increased along the corticopapillary axis. An efflux of all osmolytes (-50%) was observed in homogenates of outer and inner medulla after acute furosemide diuresis (15 min, urinary osmolality = 329 mosmol/kgH2O) and for both polyols in microdissected tubules (30 min). In urinary bladder, only low concentrations of myo-inositol were found not to be affected by furosemide treatment. Chronic lithium treatment (7 days; urinary osmolality = 385 mosmol/kgH2O) decreased inner medullary but not outer medullary osmolyte concentrations. The results confirm a site-specific organic osmolyte pattern along the rat nephron, which is rapidly changed in a segment-specific way by different mechanisms of diuresis. The bladder epithelium does not accumulate organic osmolytes because no "osmotic gap" exists across the basolateral membrane. The osmotic difference across the apical membrane is maintained by the apical tightness of these cells.