Activation of mitogen-activated protein kinases (p38-MAPKs, SAPKs/JNKs and ERKs) by adenosine in the perfused rat heart.
Adenosine and mitogen-activated protein kinases (MAPKs) have been separately implicated in cardiac ischaemic preconditioning. We investigated the activation of MAPK subfamilies by adenosine in perfused rat hearts. p38-MAPK was rapidly phosphorylated and activated (10-fold activation, maximal at 5 min) by 10 mM adenosine, as was the p38-MAPK substrate, MAPKAPK2 (4.5-fold). SAPKs/JNKs were activated (5-fold) and ERKs were phosphorylated (both maximal at 5 min). The concentration dependences of activation of p38-MAPK and ERKs were biphasic with a 'high affinity' component (maximal at 10-100 microM adenosine) and a 'low affinity' component that had not saturated at 10 mM. SAPKs/JNKs were activated only by 10 mM adenosine. These results are consistent with MAPK involvement in adenosine-mediated ischaemic preconditioning.
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NHLI Division (Cardiac Medicine), Imperial College School of Medicine, London, UK.
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Sugden
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D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000241:Adenosine