Adenosine attenuates calcium paradox injury: Role of adenosine A₁ receptor

The present study was conducted to test the hypothesis that adenosine attenuates the Ca²⁺ paradox (PD) injury via stimulation of adenosine A₁ receptors linked to G(i) proteins in the isolated rat heart. Treatment of adenosine reduced maximum lactate dehydrogenase release and ATP loss compared with regular Ca²⁺ PD. Recovery of mechanical activity after Ca²⁺ repletion was observed only in heart treated with adenosine before and during the Ca²⁺ PD. Significant preservation of myocytes was observed in adenosine-treated hearts compared with the regular Ca²⁺ PD. Adenosine exerted its effects in a dose-dependent manner, being maximum at 100 μM. The protective effects were mediated by adenosine A₁ receptor activation since the adenosine A₁ receptor agonist N⁶-phenylisopropyladenosine provided protection similar to adenosine-treated heart and was blocked by A₁ receptor antagonist and pertussis toxin. This study suggests that protection by adenosine against the lethal injury of the Ca²⁺ PD is mediated by adenosine A₁ receptor and a pertussis toxin-sensitive inhibiting G protein.