Role of ouabain-like compound in the regulation of transmembrane sodium and potassium gradients in rats.
A major biologically active Na,K-ATPase inhibitor in the mammalian body may be ouabain-like compound. We investigated the potential roles of circulating ouabain-like compound in the regulation of Na+ and K+ homeostasis in terms of Na+ and K+ distribution between the cells and the extracellular fluid (internal balance). First, we developed a population of rats immunized against ouabain to block the action of ouabain-like compound. We measured plasma and intracellular Na+ and K+ concentrations in skeletal muscle and determined Na+ (extracellular-to-intracellular concentration ratio) and K+ (intracellular-to-extracellular concentration ratio) gradients in immune rats. We examined also the ability to respond to hypertonic NaCl load in immune rats. Consistent lower plasma K+ levels and steeper Na+ and K+ gradients were observed in immune rats. K+ handling in response to hypertonic NaCl load was altered, and lower plasma K+ level was maintained in immune rats. Second, we used PST-2238, a newly developed anti-ouabain agent, to block the action of ouabain-like compound and examined its effect on plasma Na+ and K+ concentrations. Chronic administration of PST-2238 significantly lowered plasma K+ levels in rats with subtotal nephrectomy. These findings collectively suggest that ouabain-like compound may determine at least in part the internal Na+ and K+ distribution and the transmembrane cation gradients in vivo in rats.
Goto
A
A
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Yamada
K
K
Nagoshi
H
H
Dan
Y
Y
Omata
M
M
D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D015551:Autoimmunity; D002462:Cell Membrane / Q000378:metabolism; D007114:Immunization; D008297:Male; D010042:Ouabain / Q000276:immunology*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000502:physiology*
D000732:Androstanols; D012462:Saline Solution, Hypertonic; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; C106263:rostafuroxin; D011188:Potassium