Anales RANF

S2-03 ADENOSINE RECEPTORS AS A PRIMARY TARGET FOR RESVERATROL: FROM ANTITUMORAL TO NEUROPROTECTION ACTION A. Sánchez-Melgar 1 , J.L. Albasanz 1 , V. Palomera-Ávalos 2 , N. Saleh 3 , R. Guixà- González 4 , J. Selent 5 , M. Pallàs 2 , M. Martín 1 1 University of Castilla La-Mancha, Ciudad Real, Spain; 2 University of Barcelona, Spain; 3 University of Copenhagen, Denmark; 4 Autonomous University of Barcelona, Spain; 5 Pompeu Fabra University, Barcelona, Spain. Resveratrol (RSV) is a natural polyphenolic compound produced by plants under stressful conditions that has shown multiple beneficial properties for human health. However, the precise mode of action of this phytochemical remain still unclear. Therefore, we aimed to investigate whether RSV was able to induce modulation on adenosine-mediated signaling in rat C6 glioma cells. Our biochemical and computational analysis showed that RSV directly binds to adenosine receptors and acts as a non-selective agonist on these receptors. RSV-induced receptor activation can stimulate or inhibit adenylyl cyclase (AC) activity in a concentration dependent manner. RSV also modulates adenosine receptors, affecting gene expression, receptor levels, and the downstream AC pathway. Furthermore, RSV caused C6 cells growth inhibition in a time- and concentration-dependent manner. As adenosinergic system has been involved in cancer cell proliferation, we might hypothesize that RSV could induce inhibition of tumor cell growth through binding and modulation of adenosinergic system. On the other hand, long-term diet supplementation with RSV induced changes on gene expression as well as transduction pathways mediated by adenosine receptors in brain from SAMP8 mice, an animal model of aging and Alzheimer’s disease. RSV increased levels of A 1 receptor and potentiated its transduction-mediated pathway, whereas no changes on A 2A receptors were detected. Yet, A 2A receptor-mediated signaling was desensitized after RSV treatment -. In addition, the adenosine converting enzymes, 5’- Nucleotidase and Adenosine Deaminase, were found to be significantly reduced in RSV-treated mice, suggesting an alteration on adenosine metabolism. In conclusion, beneficial effect of RSV could be mediated by direct activation and modulation of adenosine receptors. Therefore, new therapeutic strategies involving resveratrol and adenosine receptors should be aimed in the future for a variety of diseases such as cancer and neurodegeneration.