Adenosine stimulates NA/K ATPase and prolongs survival in hemorrhagic shock

Hemorrhagic shock leads to the appearance of substances in plasma that can change Na/K ATPase activity. Our laboratory has reported the existence of a plasma inhibitor of Na/K ATPase that appears during shock. Recently, we have isolated a substance in plasma that stimulates Na/K ATPase.

Using liquid chromatography, we found a fraction of plasma that simulated Na/K ATPase. The purified substance was identified as adenosine by its UV spectrum. Na/K ATPase activity was assessed using 86Rb uptake in erythrocytes.

Plasma from rat, dog, and calf stimulated Na/K ATPase activity in a dose-dependent manner and this stimulation was inhibited by ouabain. Commercial adenosine also stimulated Na/K ATPase in a dose-dependent manner and was inhibited by ouabain. Na/K ATPase was not stimulated by ATP, ADP, AMP adenine, hypoxanthine, xanthine or uric acid. Stimulation by adenosine (1 mmol/L) was not affected by adenosine receptor antagonists, caffeine (1 mmol/L) or aminophylline (1 mmol/L). However, the stimulation was inhibited by the nucleoside transport blocker, dipyridamole, suggesting that adenosine acts inside the cell. Adenosine (0.5 mmol/L) given to rats in hemorrhagic shock survived longer suggesting that stimulation of Na/K ATPase prolongs survival during hemorrhagic shock.

Adenosine stimulates Na/K ATPase and prolongs survival in hemorrhagic shock, possible by reversing or overcoming the effects of an endogenous inhibitor of Na/K ATPase, as it does for ouabain. The effect of adenosine on Na/K ATPase is not mediated through adenosine receptors and probably results from an intracellular process.