Morphine postconditioning protection against reperfusion injury: PKC epsilon and extracellular signal-regulated kinase 1 and 2

The purpose of this study was to determine whether protein kinase C-epsilon (PKCε) and extracellular signal-regulated kinase (ERK) 1/2 were involved in morphine postconditioning (MpostC) in isolated rat hearts. The isolated rat hearts were randomly assigned into one of the following groups. Hearts in the time control (TC) group were constantly perfused with K-H buffer for 105 min. Hearts in the ischemia-reperfusion (I/R) group were subjected to 45 min of ischemia followed by 1 h of reperfusion. MpostC was induced by 10 min of morphine administration at the onset of reperfusion. In the other four groups, εV1-2 and PD98059 were administered with or without morphine during the first 10 min of reperfusion following the 45 min of ischemia. I/R injury was assessed by functional parameters, creatine kinase-MB (CK-MB) release and infarct size (IS/AAR). Additional hearts were excised at 20 min following reperfusion in all groups to detect PKCε activation and ERK1/2 phosphorylation. MpostC markedly reduced CK-MB release and IS/AAR, and improved cardiac functional recovery. However, these protective effects were partly abolished in the presence of either εV1-2 or PD98059. The membrane translocation of PKCε and the phosphorylation of ERK1/2 were increased in the I/R hearts, and further enhanced by MpostC. εV1-2, whether used alone or together with morphine, eliminated translocation of PKCε. The phosphorylation ERK1/2 was also abolished in the presence of εV1-2 or PD98059, which was also administered either individually or together with morphine. These findings suggested that morphine postconditioning protected isolated rat hearts against ischemia-reperfusion injury via the recruitment of the PKCε-ERK1/2 signaling pathway.