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 Gi 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 microM. 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.
Suleiman
J
J
Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Ohio 45267-0529, USA.
Ashraf
M
M
D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000172:deficiency* / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D007425:Intracellular Membranes / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology*
D018047:Receptors, Purinergic P1; D010660:Phenylisopropyladenosine; D000255:Adenosine Triphosphate; D000241:Adenosine; D002118:Calcium