Dipyridamole activates adenosine A2B receptor and AMPK/cAMP signaling and promotes myogenic differentiation of myoblastic C2C12 cells

Introduction : Sarcopenia is defined as a loss of muscle mass and strength. ATP homeostasis crucial during myogenesis. We determined how the purinergic system modulates myogenesis using dipyridamole (blocks adenosine taken up by cells) tenofovir (inhibits release) in myoblast cell line. Methods: C2C12 cells were differentiated presence/absence tenofovir/dipyridamole, with/without A2B selective inhibitor PSB-603. Extra-/intracellular nucleotides examined via HPLC. The expression differentiation proteins (Pax7, Mif5, MyoD, MyoG, MHC), PKA/CREB, receptors (A1, A2A, A2B, A3), ATP-channel pannexin-1 P2X7 receptor was analyzed WB RT-PCR. cAMP AMPK activation measured. Results: Tenofovir increased intracellular reduced extracellular adenosine, decreasing Pax7 increasing MHC prematurely. Dipyridamole AMP counteracting premature promoted tenofovir. All expressed with dipyridamole, expression. maintained inactive decreased levels, well PKAα pCREB expression, which recovered dipyridamole. Discussion: Adenosine act mediators blockade release promotes myogenesis, cAMP/AMPK pathways. Therefore, might be interest therapeutic approach sarcopenia.