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New Findings: What is the central question of this study?The aim was to investigate the role of μ‐opioid receptors in acute respiratory distress syndrome and whether their protective effect is mediated via the PI3K/Akt signalling pathway.What is the main finding and its importance?Our findings show that activation of μ‐opioid receptors ameliorates lung injury, and the effects are reversed by the PI3K inhibitor, wortmannin. The main pathology of acute respiratory distress syndrome (ARDS) is the accumulation of inflammatory cells in the lung and increased permeability of vascular endothelial cells. The μ‐opioid receptor (MOR) is a G‐protein‐coupled receptor, which stimulates angiogenesis and vascular endothelial cell proliferation. In addition, the MOR inhibits cell apoptosis via the PI3K/Akt signalling pathway. In this study, we aimed to explore the contribution of the MOR in ARDS and whether its effects are mediated via PI3K/Akt signalling. An ARDS model was established by intratracheal instillation of 5 mg kg−1 lipopolysaccharide (LPS). Lung injury was confirmed by Haematoxylin and Eosin staining, lung wet/dry weight ratio, bronchoalveolar lavage fluid protein concentrations, myeloperoxidase activity and vascular cell adhesion molecule 1 expression. Lung inflammation was determined by assessment of interleukin‐1β and tumour necrosis factor‐α concentrations. The protein level of p‐Akt was detected by western blot. Endomorphin‐1‐activated MORs attenuated LPS‐induced lung injury, lung wet/dry weight ratio, bronchoalveolar lavage fluid protein concentrations, myeloperoxidase activity, interleukin‐1β and tumour necrosis factor‐α levels and vascular cell adhesion molecule 1 expression, and elevated LPS‐induced decreased p‐Akt expression. However, the protective effect of MOR activation on lung injury was reversed by the PI3K inhibitor, wortmannin. In conclusion, MOR involvement in LPS‐induced ARDS is via the PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? What are the effects of protein kinase C (PKC) and Ca2+-calmodulin-dependent protein kinase II (CaMKII) on late sodium current ( INaL), reverse Na+-Ca2+ exchange current (reverse INCX) or intracellular Ca2+ levels changed by ouabain?, What is the main finding and its importance? Ouabain, even at low concentrations (0.5-8.0 μ m), can increase INaL and reverse INCX, and these effects may contribute to the effect of the glycoside to increase Ca2+ transients and contractility. Both PKC and CaMKII activities may mediate or modulate these processes., It has been reported that the cardiac glycoside ouabain can increase the late sodium current ( INaL), as well as the diastolic intracellular calcium concentration and contractile shortening. Whether an increase of INaL participates in a pathway that can mediate the positive inotropic response to ouabain is unknown. We therefore determined the effects of ouabain on INaL, reverse Na+-Ca2+ exchange current (reverse INCX), intracellular Ca2+ ([Ca2+]i) levels and contractile shortening in rabbit isolated ventricular myocytes. Ouabain (0.1-8 μ m) markedly increased INaL and reverse INCX in a concentration-dependent manner, with significant effects at concentrations as low as 0.5 and 1 μ m. These effects of ouabain were suppressed by the INaL inhibitors TTX and ranolazine, the protein kinase C inhibitor bisindolylmaleimide and the Ca2+-calmodulin-dependent protein kinase II inhibitor KN-93. The enhancement by 0.5 μ m ouabain of ventricular myocyte contractility and intracellular Ca2+ transients was suppressed by 2.0 μ m TTX. We conclude that ouabain, even at low concentrations (0.5-8.0 μ m), can increase INaL and reverse INCX, and these effects may contribute to the effect of the glycoside to increase Ca2+ transients and contractility. Both protein kinase C and Ca2+-calmodulin-dependent protein kinase II activities may mediate or modulate these processes. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study? What are the effects of protein kinase C (PKC) and Ca(2+) -calmodulin-dependent protein kinase II (CaMKII) on late sodium current (INaL ), reverse Na(+) -Ca(2+) exchange current (reverse INCX ) or intracellular Ca(2+) levels changed by ouabain? What is the main finding and its importance? Ouabain, even at low concentrations (0.5-8.0 μm), can increase INaL and reverse INCX , and these effects may contribute to the effect of the glycoside to increase Ca(2+) transients and contractility. Both PKC and CaMKII activities may mediate or modulate these processes. It has been reported that the cardiac glycoside ouabain can increase the late sodium current (INaL ), as well as the diastolic intracellular calcium concentration and contractile shortening. Whether an increase of INaL participates in a pathway that can mediate the positive inotropic response to ouabain is unknown. We therefore determined the effects of ouabain on INaL , reverse Na(+) -Ca(2+) exchange current (reverse INCX ), intracellular Ca(2+) ([Ca(2+) ]i ) levels and contractile shortening in rabbit isolated ventricular myocytes. Ouabain (0.1-8 μm) markedly increased INaL and reverse INCX in a concentration-dependent manner, with significant effects at concentrations as low as 0.5 and 1 μm. These effects of ouabain were suppressed by the INaL inhibitors TTX and ranolazine, the protein kinase C inhibitor bisindolylmaleimide and the Ca(2+) -calmodulin-dependent protein kinase II inhibitor KN-93. The enhancement by 0.5 μm ouabain of ventricular myocyte contractility and intracellular Ca(2+) transients was suppressed by 2.0 μm TTX. We conclude that ouabain, even at low concentrations (0.5-8.0 μm), can increase INaL and reverse INCX , and these effects may contribute to the effect of the glycoside to increase Ca(2+) transients and contractility. Both protein kinase C and Ca(2+) -calmodulin-dependent protein kinase II activities may mediate or modulate these processes., (© 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.)