Molecular Biology

, Volume 50, Issue 2, pp 200–212 | Cite as

Adenosine A2A receptor as a drug target for treatment of sepsis

  • K. V. SivakEmail author
  • A. V. Vasin
  • V. V. Egorov
  • V. B. Tsevtkov
  • N. N. Kuzmich
  • V. A. Savina
  • O. I. Kiselev


Sepsis is a generalized infection accompanied by response of the body that manifests in a clinical and laboratory syndrome, namely, in the systemic inflammatory response syndrome (SIRS) from the organism to the infection. Although sepsis is a widespread and life-threatening disease, the assortment of drugs for its treatment is mostly limited by antibiotics. Therefore, the search for new cellular targets for drug therapy of sepsis is an urgent task of modern medicine and pharmacology. One of the most promising targets is the adenosine A2A receptor (A2AAR). The activation of this receptor, which is mediated by extracellular adenosine, manifests in almost all types of immune cells (lymphocytes, monocytes, macrophages, and dendritic cells) and results in reducing the severity of inflammation and reperfusion injury in various tissues. The activation of adenosine A2A receptor inhibits the proliferation of T cells and production of proinflammatory cytokines, which contributes to the activation of the synthesis of anti-inflammatory cytokines, thereby suppressing the systemic response. For this reason, various selective A2AAR agonists and antagonists may be considered to be drug candidates for sepsis pharmacotherapy. Nevertheless, they remain only efficient ligands and objects of pre-clinical and clinical trials. This review examines the molecular mechanisms of inflammatory response in sepsis and the structure and functions of A2AAR and its role in the pathogenesis of sepsis, as well as examples of using agonists and antagonists of this receptor for the treatment of SIRS and sepsis.


sepsis systemic inflammatory response syndrome adenosine adenosine A2A receptors agonists and antagonists of adenosine receptors 



multiple organ failure




adenosine A2A receptor


adenylate cyclase


activator protein 1


adenosine receptor


cluster of differentiation (of lymphocytes)


cell division control protein 42 homolog


CCAAT-enhancer-binding protein


cycloxygenase of type 2


cAMP responsive element binding protein 1


cytotoxic T-lymphocyte-associated antigen 4


chemokine (C-X-C motif) ligand 1


endothelial NO synthase


granulocyte colony-stimulating factor


G-protein-coupled receptor


intercellular adhesion molecule 1






inducible NO synthase


inositol 3,4,5-triphosphate


mitogen-activated protein kinase


macrophage colony-stimulating factor


multiple organ failure


nuclear factor κB


NO synthase


platelet activating factor


plasminogen activator inhibitor-1


guanine nucleotide exchange factor containing PDZ-domain


prostaglandin E2


phosphoinositide 3-kinase


phosphatidylinositol 4,5-diphosphate


protein kinase A

PKB (or Akt)

protein kinase B


protein kinase С-zeta


systemic inflammatory response syndrome


small ubiquitin-related modifier 1


tissue factor III (thromboplastin)


transforming growth factor beta


Toll-like receptors


tumor necrosis factor α


translin-associated factor X


ubiquitin specific protease 4


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Copyright information

© Pleiades Publishing, Inc. 2016

Authors and Affiliations

  • K. V. Sivak
    • 1
    Email author
  • A. V. Vasin
    • 1
    • 2
  • V. V. Egorov
    • 1
  • V. B. Tsevtkov
    • 1
  • N. N. Kuzmich
    • 1
  • V. A. Savina
    • 1
  • O. I. Kiselev
    • 1
  1. 1.Research Institute of InfluenzaMinistry of Health of the Russian FederationSt. PetersburgRussia
  2. 2.St. Petersburg State Polytechnical UniversitySt. PetersburgRussia

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