Activation of ERK and suppression of calcineurin are interacting mechanisms of cardioprotection afforded by delta-opioid receptor activation

Basic Research in Cardiology
Yoshihiro IkedaKazuaki Shimamoto

Abstract

The aim of this study was to examine possible interactions of ERK and calcineurin in cardioprotection afforded by delta-opioid receptor stimulation. Infarction was induced in rat hearts by 20-min coronary occlusion and reperfusion. Tissue ERK level and calcienurin activity were determined by immunoblotting and an assay using a phosphopeptide substrate, respectively. Administration of a delta-opioid receptor agonist, D-Ala2-D-Leu5-enkephalin (DADLE, 1 mg/kg), before ischemia increased the phospho-ERK levels during ischemia and reduced infarct size (as percentage of risk area, %IS/AR) from 47.7 +/- 2.3% to 23.2 +/- 2.5%. This protection was abolished by 10 mg/kg of natrindole hydrochloride (NTI), a delta-opioid receptor antagonist. PD98059, a MEK1/2 inhibitor, abolished both ERK1/2 activation and infarct size limitation by DADLE. Calcineurin inhibitors, cyclosporine-A (5 mg/kg) and FK506 (3.5 mg/kg), reduced %IS/AR (27.4 +/- 4.4% and 29.9 +/- 3.4%, respectively). The protective effects of these calcineurin inhibitors were inhibited by PD98059, and the combination of DADLE with cyclosporine-A or FK506 did not afford further cardioprotection. DADLE significantly suppressed myocardial calcineurin activity, and this effect was inhibi...Continue Reading

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Citations

Oct 15, 2013·European Journal of Pharmacology·Stylianos DragasisTheodoros Xanthos
Jun 5, 2012·Journal of Molecular and Cellular Cardiology·Kaori Shintani-IshidaKen-Ichi Yoshida
Oct 24, 2007·Peptides·Richard J Bodnar
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May 22, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Tetsuji MiuraKazuaki Shimamoto
Jun 4, 2020·Journal of Cellular and Molecular Medicine·Derek J HausenloyFabio Di Lisa

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