THE IMPACT OF ADENOSINE A2B RECEPTORS MODULATION ON PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA CO-ACTIVATOR 1-ALPHA AND TRANSCRIPTION FACTORS

Previous studies have demonstrated that the activation of adenosine A2B receptors increases adenosine 3′-cyclic monophosphate (cAMP) accumulation in rat skeletal muscle cells, which is probably an important yet unknown mechanism contributing to the regulation of skeletal muscle functions. via rat L6 skeletal muscle cells, it has been elucidated further potential molecular signaling responsible for adenosine A2B receptor modulations via quantitative real-time PCR assays (probe-based). The results of the present study has shown for the first time that NECA alters the expression of PGC-1α significantly in both one week and 19 hours starved skeletal muscle cells (P<0.05 and P<0.01, respectively) (2.5 and -0.58 fold change compared to vehicle, respectively). Adenosine A2B receptors mediate NECA-modulated PGC-1α mRNA gene expression in skeletal muscle cells. To our knowledge, this is the first study demonstrating an induction of PGC-1α gene by CGS 21680 significantly (P<0.001) (around 1.8 fold change compared to vehicle). In the current study, NECA (10 μM) increases NR4A1 and NR4A3 mRNA gene expression significantly (P<0.05) (around 2.7 and 5.2 -fold change to vehicle, respectively), which are blocked by a selective adenosine A2B receptor antagonist, PSB 603. This current study identifies the adenosine A2B receptors as a significant regulator of PGC-1α, NR4A1 and NR4A3 mRNA gene expression in skeletal muscle, thereby pointing to its therapeutic potential. In summary, it has been observed the selective, potentially functional expression of adenosine A2 receptors in skeletal muscle cells. Whether adenosine A2 receptor mediated functional responses play a role in skeletal muscle pathophysiology is yet to be elucidated.