A novel sorbitol transport mechanism in cultured renal papillary epithelial cells.
The renal papillary epithelial cell line, GRB-PAP1, accumulates sorbitol when grown in a hypertonic (500 mosmol/kgH2O) bathing medium. When the cells are returned to a 300 mosmol/kgH2O medium, they lose their sorbitol rapidly to the bath. Sorbitol movement across the membranes of these cells was investigated by studying the uptake of radioactive sorbitol and related compounds. Sorbitol uptake increased 71-fold when cells grown in 500 mosmol/kgH2O medium were exposed to a 300 mosmol/kgH2O test solution. The magnitude of the permeability increase was proportional to the size of the change in the osmolality of the bathing medium and not the absolute osmolality. Sorbitol uptake was a linear function of medium sorbitol concentration with no sign of saturation at sorbitol concentrations up to 315 mM. Although the permeability of other polyols was increased when the osmolality was reduced, competition between sorbitol and related sugars and polyols could not be demonstrated. Both the increased sorbitol uptake after a decrease in medium osmolality and the decrease to control permeability after return to the original osmolality were complete within 30 s. A wide variety of transport inhibitors and ion substitutions failed to alter the magnitude of the sorbitol permeability increase. The most effective inhibitor was quinidine, 1 mM reducing sorbitol uptake by 73%. The sorbitol permeability increase could also be blocked by reducing the temperature to 0 degrees C. Nonspecific uptake of sorbitol, such as endocytosis, was shown to be of only minor significance. The large increase in sorbitol permeability and subsequent sorbitol efflux enables these cells to withstand large decreases in osmolality without excessive swelling and consequent damage. A similar compensatory mechanism may operate in vivo in the renal papilla during the onset of diuresis.
Siebens
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AW
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892.
Spring
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KR
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002250:Carbon Radioisotopes; D002460:Cell Line; D004232:Diuretics / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D004376:Galactitol / Q000494:pharmacology; D007294:Inositol / Q000494:pharmacology; D007679:Kidney Medulla / Q000378:metabolism*; D007700:Kinetics; D008353:Mannitol / Q000494:pharmacology; D009994:Osmolar Concentration; D000073718:Pancreatitis-Associated Proteins; D011865:Radioisotope Dilution Technique; D013012:Sorbitol / Q000378:metabolism*; D013395:Sucrose / Q000378:metabolism / Q000494:pharmacology
D002250:Carbon Radioisotopes; D004232:Diuretics; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D004376:Galactitol; D008353:Mannitol; D007294:Inositol; D013012:Sorbitol; D013395:Sucrose