title: [Adenosine A2A receptor as a drug target for treatment of sepsis].
abstract: 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 A(2A) receptor (A(2A)AR). 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 A(2A) 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 A(2A)AR 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 A(2A)AR 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.
authors.affiliation: Research Institute of Influenza, Ministry of Health of the Russian Federation, St. Petersburg, 197376, Russia.|konstantin.sivak@influenza.spb.ru.
authors.forename: K V
authors.initials: KV
authors.lastname: Sivak
authors.affiliation: Research Institute of Influenza, Ministry of Health of the Russian Federation, St. Petersburg, 197376, Russia.|St. Petersburg State Polytechnical University, St. Petersburg, 195251, Russia.
authors.forename: A V
authors.initials: AV
authors.lastname: Vasin
authors.affiliation: Research Institute of Influenza, Ministry of Health of the Russian Federation, St. Petersburg, 197376, Russia.
authors.forename: V V
authors.initials: VV
authors.lastname: Egorov
authors.affiliation: Research Institute of Influenza, Ministry of Health of the Russian Federation, St. Petersburg, 197376, Russia.
authors.forename: V B
authors.initials: VB
authors.lastname: Tsevtkov
authors.affiliation: Research Institute of Influenza, Ministry of Health of the Russian Federation, St. Petersburg, 197376, Russia.
authors.forename: N N
authors.initials: NN
authors.lastname: Kuzmich
authors.affiliation: Research Institute of Influenza, Ministry of Health of the Russian Federation, St. Petersburg, 197376, Russia.
authors.forename: V A
authors.initials: VA
authors.lastname: Savina
authors.affiliation: Research Institute of Influenza, Ministry of Health of the Russian Federation, St. Petersburg, 197376, Russia.
authors.forename: O I
authors.initials: OI
authors.lastname: Kiselev
mesh_terms: D000241:Adenosine / Q000627:therapeutic use; D058908:Adenosine A2 Receptor Agonists / Q000378:metabolism* / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D058990:Molecular Targeted Therapy; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D018805:Sepsis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D058908:Adenosine A2 Receptor Agonists; D043705:Receptor, Adenosine A2A; D000241:Adenosine
keywords: Sepsis; adenosine; adenosine A2A receptors; agonists and antagonists of adenosine receptors; systemic inflammatory response syndrome