Adenosine A 2B receptors modulate cAMP levels and induce CREB but not ERK1/2 and p38 phosphorylation in rat skeletal muscle cells

• Published in: Biochemical and biophysical research communications Vol. 307; no. 1; pp. 180 - 187
• Main Authors: Lynge, Jan, Schulte, Gunnar, Nordsborg, Nikolai, Fredholm, Bertil B, Hellsten, Ylva
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2003
• Subjects: Adenosine - analogs & derivatives; Adenosine - metabolism; Adenosine-5'-(N-ethylcarboxamide) - metabolism; Animals; Cells, Cultured; Cyclic AMP - metabolism; Cyclic AMP response element binding protein; Cyclic AMP Response Element-Binding Protein - genetics; Cyclic AMP Response Element-Binding Protein - metabolism; Extracellular signal-regulated protein kinase 1 and 2; Medicin och hälsovetenskap; Mitogen-activated protein kinase; Mitogen-Activated Protein Kinase 1 - genetics; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; p38 Mitogen-Activated Protein Kinases; Pertussis Toxin - metabolism; Phenethylamines - metabolism; Phosphorylation; Rats; Receptor, Adenosine A2A; Receptor, Adenosine A2B; Receptors, Purinergic P1 - genetics; Receptors, Purinergic P1 - metabolism; RNA - metabolism; Stress-activated protein kinase; Transcription factor; Triazines - metabolism; Triazoles - metabolism; Mitogen-activated protein kinase; Stress-activated protein kinase; Transcription factor; Extracellular signal-regulated protein kinase 1 and 2; Cyclic AMP response element binding protein
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(03)01125-2

The present study examined the existence of the adenosine
A
1,
A
2
A
,
and A
2B receptors and the effect of receptor activation on cAMP accumulation and protein phosphorylation in primary rat skeletal muscle cells. Presence of mRNA and protein for all three receptors was demonstrated in both cultured and adult rat skeletal muscle. NECA (10
−9–10
−4
M) increased the cAMP concentration in cultured muscle cells with an EC
50 of (95% confidence interval)=15 (5.9–25.1)
μM, whereas CGS 21680 (10
−9–10
−4
M) had no effect on cAMP accumulation. Concentrations of [R]-PIA below 10
−6
M had no effect on cAMP accumulation induced by either isoproterenol or forskolin. NECA resulted in phosphorylation of CREB with an EC
50 of (95% confidence interval)=1.7 (0.40–7.02)
μM, whereas ERK1/2 and p38 phosphorylation was unchanged. The results show that, although the
A
1,
A
2
A
,
and A
2B receptors are all present in skeletal muscle cells, the effect of adenosine on adenylyl cyclase activation and phosphorylation of CREB is mainly mediated via the adenosine A
2B receptor.