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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Darlington
Daniel N
DN
Department of Surgery, and The R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ddarlington@smail.umaryland.edu
Gann
Donald S
DS
D000241:Adenosine / Q000097:blood / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006801:Humans; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D012414:Rubidium Radioisotopes; D012771:Shock, Hemorrhagic / Q000097:blood*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D012414:Rubidium Radioisotopes; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D000241:Adenosine