Abstract

The present study summarizes the biological effects elicit upon A3 adenosine receptor (A3AR) activation in normal and tumor cells. Anti-inflamatory response is mediated upon A3AR activation in neutrophils, eosinophils and macrophages via direct effect on cell degranulation or the production of anti-inflamatory cytokines. In basophils, which highly express A3AR, degranulation and mediator release upon receptor activation lead to pro-inflammatory effects resulting in bronchospasm and asthma. In other normal cells such as cardiomyocytes, neuronal cells and bone marrow cells A3AR activation induces cytoprotective effects in vitro. In vivo, A3AR agonists act as cardio- and neuroprotective agents and attenuate ischemic damage. Furthermore, agonists to A3AR induce granulocyte colony stimulating factor (G-CSF) production and myeloprotective effect in chemotherapy treated mice. Interestingly, A3AR agonists inhibit tumor cell growth both in vitro and in vivo through a cytostatic effect mediated via the de-regulation of the Wnt signaling pathway. The variety of activities elicit by A3AR agonists suggest their potential use as therapeutic agents in inflammation, brain / cardiac ischemia and cancer. Antagonists to A3AR may be implemented to the therapy of asthma and additional allergic conditions.

Keywords: adenosine, adenosine receptor, cancer therapy, myeloprotection, cardioprotection, neuroprotection, antiinflammatory, asthma