Background: Activation of the adenosine A2B receptor (A2BR) can reduce myocardial ischemia/reperfusion (IR) injury. However, the mechanism underlying the A2BR-mediated cardioprotection is less clear. The present study was designed to investigate the potential mechanisms of cardioprotection mediated by A2BR.
Methods And Results: C57BL/6 mice underwent 40-minute ischemia and 60-minute reperfusion. ATL-801, a potent selective A2BR antagonist, could not block ischemic preconditioning induced protection. BAY 60-6583, a highly selective A2BR agonist, significantly reduced myocardial infarct size, and its protective effect could be blocked by either ATL-801 or wortmannin. BAY 60-6583 increased phosphorylated Akt (p-Akt) levels in the heart at 10 min of reperfusion, and this phosphorylation could also be blocked by ATL-801 or wortmannin. Furthermore, BAY 60-6583 significantly increased M2 macrophages and decreased M1 macrophage and neutrophils infiltration in reperfused hearts, which also could be blocked by wortmannin. Meanwhile, confocal imaging studies showed that the majority of Akt phosphorylation in the heart was colocalized to CD206+ cells in both control and BAY 60-6583 pretreated hearts.
Conclusion: Our results indicated that pretreatment with BAY 60-6583 protects the heart against myocardial IR injury by its anti-inflammatory effects, probably by modulating macrophages phenotype switching via a PI3K/Akt pathway.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486757 | PMC |
| http://dx.doi.org/10.1155/2015/585297 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The different effects of four adenosine receptors in liver fibrosis.
Front Pharmacol
September 2024
Department of Obstetrics and Gynecology, Hainan Branch of PLA General Hospital, Sanya, China.
Article Synopsis
- The study investigates the roles of different adenosine receptors (A1R, A2AR, A2BR, A3R) in liver fibrosis, noting that A1R and A2AR may worsen the condition while A2BR and A3R could help alleviate it.
- Using mouse models of liver fibrosis, various adenosine receptor agonists were tested, showing that A1R and A2AR activation increases liver damage and cellular proliferation, whereas A2BR and A3R activation helps reduce fibrosis symptoms.
- The findings indicate that targeting specific adenosine receptors could be a potential therapeutic strategy for managing liver fibrosis, with NECA, an adenosine analog, showing promising results in reducing fibrosis and
Adenosine A receptors differently modulate oligodendrogliogenesis and myelination depending on their cellular localization.
Glia
November 2024
Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
Differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs) is a key event for axonal myelination in the brain; this process fails during demyelinating pathologies. Adenosine is emerging as an important player in oligodendrogliogenesis, by activating its metabotropic receptors (AR, AR, AR, and AR). We previously demonstrated that the Gs-coupled AR reduced differentiation of primary OPC cultures by inhibiting delayed rectifier (I) as well as transient (I) outward K currents.
View Article and Find Full Text PDFComparison of the Genomic Activity of an EP-Receptor and β-Adrenoceptor Agonist in BEAS-2B Human Bronchial Epithelial Cells: In Search of Compartmentalized, cAMP-Dependent Gene Expression.
J Pharmacol Exp Ther
September 2024
Lung Health Research Group, Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
It has been proposed that inhaled E-prostanoid 4 (EP)-receptor agonists could represent a new class of bronchodilators for the treatment of asthma that are as effective as -adrenoceptor agonists. However, the genomic impact of such drugs is unknown despite being potentially deleterious to respiratory health. Herein, we used mRNA-seq to compare the transcriptomic responses produced by 2-[3-[(1R,2S,3R)-3-hydroxy-2-[(E,3S)-3-hydroxy-5-[2-(methoxymethyl)phenyl]pent-1-enyl]-5-oxo-cyclopentyl]sulphanylpropylsulphanyl] acetic acid (ONO-AE1-329; an EP-receptor agonist) and vilanterol (a -adrenoceptor agonist) in BEAS-2B human airway epithelial cells.
View Article and Find Full Text PDFA novel and selective fluorescent ligand for the study of adenosine A receptors.
Pharmacol Res Perspect
August 2024
Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham, Nottingham, UK.
Fluorescent ligands have proved to be powerful tools in the study of G protein-coupled receptors in living cells. Here we have characterized a new fluorescent ligand PSB603-BY630 that has high selectivity for the human adenosine A receptor (AR). The AR appears to play an important role in regulating immune responses in the tumor microenvironment.
View Article and Find Full Text PDFTranslocation of Adenosine A2B Receptor to Mitochondria Influences Cytochrome P450 2E1 Activity after Acetaminophen Overdose.
Livers
March 2024
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, MS 1018, Kansas City, KS 66160, USA.
The adenosine A2B receptor (A2BAR) is a member of a family of G-protein coupled receptors (GPCRs), which has a low affinity for adenosine and is now implicated in several pathophysiological conditions. We have demonstrated the beneficial effects of A2BAR activation in enhancing recovery after acute liver injury induced by an acetaminophen (APAP) overdose. While receptor trafficking within the cell is recognized to play a role in GPCR signaling, its role in the mediation of A2BAR effects in the context of APAP-induced liver injury is not well understood.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!