Ouabain-induced lethal proximal tubule cell injury is prevented by glycine.
Exposure to 1 mM ouabain for greater than 30 min caused lethal cell injury to isolated rabbit proximal tubules as measured by increased lactate dehydrogenase release. Addition of 2 mM glycine or glutathione to the incubation medium prevented this injury and a sharp fall of cell ATP that accompanied it. Glycine and glutathione did not alter rapid, early effects of ouabain to deplete cell K+ and inhibit respiration. Preservation of cellular glutathione was not required for protection. Glycine did not ameliorate ouabain-induced increases of cell water and did not prevent lethal cell injury associated with cell swelling produced by incubation in a high K+ concentration medium. In contrast, 100 mM mannitol, which at least partially ameliorated swelling in both ouabain and high-K+ medium, prevented lethal injury in high-K+ medium and decreased it in the presence of ouabain. The combination of glycine and mannitol completely prevented ouabain-induced lethal injury and cell water increases. These observations indicate that glycine, unlike mannitol, does not protect against primary volume-induced insults. Ouabain-induced lethal cell injury results from a process that includes both a volume component ameliorated by mannitol and a volume-independent component that is prevented by glycine and is closely associated with accelerated ATP depletion.
Weinberg
J M
JM
Department of Internal Medicine, Veterans Administration Medical Center, Ann Arbor, Michigan.
Davis
J A
JA
Abarzua
M
M
Smith
R K
RK
Kunkel
R
R
D005978:Glutathione / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008353:Mannitol / Q000494:pharmacology; D009994:Osmolar Concentration; D010042:Ouabain / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D013997:Time Factors
D008353:Mannitol; D010042:Ouabain; D005978:Glutathione; D011188:Potassium; D005998:Glycine