The Impact Of Adenosine A2B Receptors Modulation On Nuclear Receptors (NR4A) Gene Expression
Mansour HaddadAssistant Professor, Department of Clinical Sciences, Faculty of Pharmacy, Philadelphia University, Jordan Corresponding Author E-mail : Dr.man.haddad@gmail.com
Abstract: Adenosine is a ubiquitous signalling molecule, of which the majority of the effects are mediated by interaction with its four G-protein-coupled receptors (A1, A2A, A2B and A3) 1. It has been proposed that adenosine modulates different functional activities in skeletal muscle cells. Previous studies have demonstrated that the activation of adenosine A2B receptors increases adenosine 3'-cyclic monophosphate (cAMP) accumulation in rat skeletal muscle cells 2, which is probably an important yet unknown mechanism contributing to the regulation of skeletal muscle functions. Using rat L6 skeletal muscle cells, I elucidate further potential molecular signalling responsible for adenosine A2B receptor modulations. Skeletal muscle cells are commonly employed cells, and have been previously described as expressing adenosine receptors 3. Quantitative real-time PCR assays (probe-based) are used to evaluate the gene expression profiles of adenosine A2B receptor signalling. In this study, I show that adenosine A2B receptors are functionally expressed in skeletal muscle cells, as indicated by the fact that the activation of adenosine A2B receptors increases the NR4A mRNA gene expression level using qRT-PCR. Previous studies have shown that the nonselective adenosine A2B receptor agonist NECA, but not the adenosine A2A receptor selective agonist CGS 21680, induces cAMP accumulations 2. The effect of NECA is blocked by the selective antagonist of adenosine A2B receptors, PSB 6032. In the current study, NECA (10μM) increases NR4A1, NR4A2 and NR4A3 mRNA gene expression significantly (a 5.9-, 2.9- and 2.4-fold change to vehicle, respectively), which are blocked by a selective adenosine A2B receptor antagonist, PSB 603 (100 nM). This current study identifies the adenosine A2B receptors as a significant regulator of NR4A mRNA gene expression in skeletal muscle, thereby pointing to its therapeutic potential. In summary, I observe the selective, potentially functional expression of adenosine A2B receptors in skeletal muscle cells. Whether adenosine A2B receptor-mediated functional responses play a role in skeletal muscle pathophysiology is yet to be elucidated.
Keywords: Adenosine A2B receptors, NECA, PSB603, CGS 21680, NR4A, skeletal muscle cells. Back to TOC