Transport defects of rabbit medullary thick ascending limb cells in obstructive nephropathy
Autor: | Subbarao V. Yalla, M. R. Sullivan, Shang-Jyh Hwang, G. Otuechere, M. Haas, Mark L. Zeidel, Michael Kashgarian, Patricio Silva, Hobart W. Harris |
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Jazyk: | angličtina |
Rok vydání: | 1993 |
Předmět: |
medicine.medical_specialty
Sodium-Potassium-Chloride Symporters Sodium chemistry.chemical_element Biological Transport Active urologic and male genital diseases Ouabain Oxygen Consumption Furosemide Reference Values Internal medicine medicine Animals Bumetanide Kidney Kidney Medulla Lagomorpha biology urogenital system Cell Membrane General Medicine biology.organism_classification NAD Obstructive Nephropathy Kinetics Endocrinology medicine.anatomical_structure chemistry Kidney Diseases Rabbits Sodium-Potassium-Exchanging ATPase Cotransporter Carrier Proteins medicine.drug Research Article Ureteral Obstruction |
Popis: | To characterize the sodium transport defect responsible for salt wasting in obstructive nephropathy, the major sodium transporters in the medullary thick ascending limb (mTAL), the apical Na-K-2Cl cotransporter and the basolateral Na-K-ATPase, were studied in fresh suspensions of mTAL cells and outer medulla plasma membranes prepared from obstructed and untreated kidneys. Oxygen consumption (QO2) studies in intact cells revealed marked reductions in the inhibitory effects of both furosemide and ouabain on QO2 in cells from obstructed, as compared with control animals, indicating a reduction in activities of both the Na-K-2Cl cotransporter and the Na-K-ATPase. Saturable [3H]bumetanide binding was reduced in membranes isolated from obstructed kidneys, but the Kd for [3H]bumetanide was unchanged, indicating a decrease in the number of functional luminal Na-K-2Cl cotransporters in obstructed mTAL. Ouabain sensitive Na-K-ATPase activity in plasma membranes was also reduced, and immunoblots using specific monoclonal antibodies directed against the alpha and beta subunits of rabbit Na-K-ATPase showed decreased amounts of both subunits in outer medullas of obstructed kidney. A significant decrease in [3H]bumetanide binding was detected after 4 h of ureteral obstruction, whereas Na-K-ATPase activity at this time was still not different from control. We conclude that ureteral obstruction reduces the amounts of both luminal Na-K-2Cl cotransporter and basolateral Na-K-ATPase in mTAL of obstructed kidney and that these reductions contribute to the salt wasting observed after release of obstruction. |
Databáze: | OpenAIRE |
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