Role of Ouabain-like Compound in the Regulation of Transmembrane Sodium and Potassium Gradients in Rats

Author:

Goto Atsuo1,Yamada Kaoru1,Nagoshi Hiroshi1,Dan Yoshiyuki1,Omata Masao1

Affiliation:

1. From the Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, and the Department of Human Dry Dock, Sanraku Hospital (K.Y.), Tokyo, Japan.

Abstract

Abstract 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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Internal Medicine

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