scholarly journals Adenosine A2A receptor stimulation potentiates nitric oxide release by activated microglia

2005 ◽  
Vol 95 (4) ◽  
pp. 919-929 ◽  
Author(s):  
Josep Saura ◽  
Ester Angulo ◽  
Aroa Ejarque ◽  
Vicent Casado ◽  
Josep M. Tusell ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Adenosine A2a Receptor ◽  
Receptor Stimulation ◽  
Nitric Oxide Release ◽  
Activated Microglia ◽  
A2a Receptor ◽  
Adenosine A2a

scholarly journals Corrigendum: Adenosine A2A Receptor Stimulation Inhibits TCR-Induced Notch1 Activation in CD8+T-Cells

2019 ◽  
Vol 10 ◽  
Author(s):  
Claudia Sorrentino ◽  
Fokhrul Hossain ◽  
Paulo C. Rodriguez ◽  
Rosa A. Sierra ◽  
Antonio Pannuti ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Adenosine A2a Receptor ◽  
Receptor Stimulation ◽  
A2a Receptor ◽  
Adenosine A2a

scholarly journals Adenosine A2A-Receptor Stimulation Inhibits Lipopolysaccharide-Induced Interleukin-18 Production in Monocytes

2007 ◽  
Vol 104 (2) ◽  
pp. 183-186 ◽  
Author(s):  
Hideo Kohka Takahashi ◽  
Toru Kanke ◽  
Keyue Liu ◽  
Tadashi Yoshino ◽  
Toshiaki Sendo ◽  
...  
Keyword(s):  
Adenosine A2a Receptor ◽  
Interleukin 18 ◽  
Receptor Stimulation ◽  
A2a Receptor ◽  
Adenosine A2a

Adenosine A2a receptor stimulation prevents hepatocyte lipotoxicity and non-alcoholic steatohepatitis (NASH) in rats

2012 ◽  
Vol 123 (5) ◽  
pp. 323-332 ◽  
Author(s):  
Chiara Imarisio ◽  
Elisa Alchera ◽  
Salvatore Sutti ◽  
Guido Valente ◽  
Francesca Boccafoschi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Critical Role ◽  
Intraperitoneal Administration ◽  
Adenosine A2a Receptor ◽  
Mitogen Activated Protein Kinase ◽  
Receptor Stimulation ◽  
Deficient Diet ◽  
Alcoholic Steatohepatitis ◽  
A2a Receptor ◽  
Adenosine A2a

NEFA (non-esterified ‘free’ fatty acid)-mediated lipotoxicity plays a critical role in the pathogenesis of NASH (non-alcoholic steatohepatitis). In the light of the growing need for new therapeutic options for NASH, we investigated the action of A2aR (adenosine A2a receptor) stimulation against lipotoxicity. The effects of the A2aR agonist CGS21680 [2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxyamidoadenosine] were evaluated ‘in vitro’ in liver cells exposed to SA (stearic acid) and ‘in vivo’ in rats with NASH induced by 8 weeks of feeding with an MCD diet (methionine/choline-deficient diet). In cultured hepatocytes, SA promoted apoptosis by inducing MKK4 (mitogen-activated protein kinase kinase 4)/SEK1 (stress-activated protein kinase/extracellular-signal-regulated kinase kinase-1) and JNK-1/2 (c-Jun N-terminal kinase-1/2) activation. CGS21680 addition prevented JNK-1/2 activation and reduced apoptosis without interfering with lipid accumulation. CGS21680 action required PI3K (phosphoinositide 3-kinase)/Akt-mediated block of MKK4/SEK1. Consistently, PI3K inhibition with wortmannin abolished the cytoprotective action of CGS21680 and reverted MKK4 inhibition. SA lipotoxicity was also prevented by transfecting HTC cells with a specific MKK4/SEK1 siRNA (small interfering RNA). In rats receiving the MCD diet, the development of NASH was associated with MKK4/SEK1 and JNK-1/2 activation. CGS21680 (0.5 mg/kg of body weight, intraperitoneal) administration to MCD-fed rats prevented JNK-1/2 activation by acting on MKK4/SEK1. CGS21680 also effectively reduced NASH-associated ALT (alanine aminotransferase) release, hepatocyte apoptosis, liver inflammation and fibrosis without affecting hepatic steatosis. Taken together, these results demonstrate that, by inhibiting JNK-1/2, A2aR stimulation reduces lipotoxicity and ameliorates NASH, giving a rationale to investigate A2aR agonists as possible new therapeutic agents in preventing fatty liver progression to NASH.

scholarly journals Adenosine A2A receptor stimulation restores cell functions and differentiation in Niemann-Pick type C-like oligodendrocytes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chiara De Nuccio ◽  
Antonietta Bernardo ◽  
Antonella Ferrante ◽  
Rita Pepponi ◽  
Alberto Martire ◽  
...  
Keyword(s):  
Adenosine A2a Receptor ◽  
Receptor Stimulation ◽  
Cell Functions ◽  
A2a Receptor ◽  
Type C ◽  
Niemann Pick ◽  
Adenosine A2a

scholarly journals Adenosine A2a Receptor Stimulation Attenuates Ischemia-Reperfusion Injury and Improves Survival in A Porcine Model of DCD Liver Transplantation

2020 ◽  
Vol 21 (18) ◽  
pp. 6747
Author(s):  
Zoltan Czigany ◽  
Eve Christiana Craigie ◽  
Georg Lurje ◽  
Shaowei Song ◽  
Kei Yonezawa ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Adenosine A2a Receptor ◽  
Large Animal Model ◽  
Large Animal ◽  
Receptor Stimulation ◽  
A2a Receptor ◽  
Htk Solution ◽  
Adenosine A2a

Orthotopic liver transplantation (OLT) using allografts from donation after circulatory death (DCD) is potentially associated with compromised clinical outcomes due to ischemia-reperfusion injury (IRI)-induced organ damage and graft-related complications. The aim of this study was to provide in vivo data on the effects of adenosine A2a receptor stimulation in a clinically relevant large animal model of DCD liver transplantation. Cardiac arrest was induced in German Landrace pigs (n = 10; 20–25 kg). After 30 min of warm ischemia, the donor liver was retrieved following a cold flush with 3 L of histidine-tryptophan-ketoglutarate-HTK solution. Animals of the treatment group (n = 5/group) received a standard dose of the selective adenosine receptor agonist CGS 21680 added to the cold flush. All grafts were stored for 4.5 h at 4 °C in HTK-solution before OLT. Hepatocellular injury, apoptosis, protein kinase A-PKA activity, graft microcirculation, liver function, and animal survival were assessed. Compared to untreated livers, adenosine A2a receptor stimulation resulted in improved tissue microcirculation (103% ± 5% vs. 38% ± 4% compared to baseline; p < 0.05), accelerated functional recovery of the graft (indocyanine green-plasma disappearance rate (ICG-PDR) of 75% ± 18% vs. 40% ± 30% after 3 h), increased PKA activity ratio (56% ± 3% vs. 32% ± 3%; p < 0.001 after 1 h), and consequently reduced tissue necrosis and apoptosis. The potent protective effects were clinically manifested in significantly improved survival in the treatment group after 72 h (100% vs. 40%; p = 0.04). The ex vivo administration of adenosine A2a receptor agonist during the back-table flush mitigates IRI-mediated tissue damage and improves functional graft recovery and survival in a large animal model of DCD liver transplantation.

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