Endogenous ouabain-like compound increases heart muscle contractility

Abstract

Cardiac glycosides such as digoxin or ouabain have long been known to influence the strength of contraction of cardiac muscle^1–3. Although the mechanism of action of these compounds remains unknown^4,5, all the proposed modes of action are based on initial binding to specific membrane receptors which are part of the (Na⁺ + K⁺) ATPase complex. These receptors, well characterized and defined^6–8, suggest the existence of an endogenous substance capable of binding to them, in analogy with endogenous opiates, discovered long after morphine and its receptors⁹. As glycosides affect (Na⁺ + K⁺)ATPase activity, an endogenous substance may be a regulator of this important enzyme. Indeed, the search for endogenous regulators of the (Na⁺ + K⁺)ATPase or ouabain-like compounds (OLC) has recently intensified. These compounds, extracted and partially purified from mammalian brain^10–14, heart¹⁵, blood^16–19 and urine^20,21, and from toad skin and plasma^22,23, have been shown to inhibit ³H-ouabain binding and (Na⁺ + K⁺)ATPase activity. We report here that in addition to these effects, the OLC, highly purified from toad skin and sheep brain, increases the force of contraction of frog and guinea pig atrium.