Adenosine A^sub 2A^ receptor as a drug target for treatment of sepsis

• Published in: Molecular biology (New York) Vol. 50; no. 2; p. 200
• Main Authors: Sivak, K V, Vasin, A V, Egorov, V V, Tsevtkov, V B, Kuzmich, N N, Savina, V A, Kiselev, O I
• Format: Journal Article
• Language: English
• Published: New York Springer Nature B.V 01.03.2016
• Subjects: Adenosine; Ligands; Molecular biology; Sepsis
• ISSN: 0026-8933; 1608-3245
• DOI: 10.1134/S0026893316020230

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^sub 2A^ receptor (A^sub 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^sub 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^sub 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^sub 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.