Adenosine A 2B receptors modulate cAMP levels and induce CREB but not ERK1/2 and p38 phosphorylation in rat skeletal muscle cells.
The present study examined the existence of the adenosine A(1),A(2A), 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) micro M, 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) micro M, whereas ERK1/2 and p38 phosphorylation was unchanged. The results show that, although the A(1),A(2A), 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.
Lynge
Jan
J
Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sports Sciences, August Krogh Institute, Copenhagen University, Universitetsparken 13, Copenhagen Ø, DK-2100, Denmark.
Schulte
Gunnar
G
Nordsborg
Nikolai
N
Fredholm
Bertil B
BB
Hellsten
Ylva
Y
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D037342:Pertussis Toxin / Q000378:metabolism; D010627:Phenethylamines / Q000378:metabolism; D010766:Phosphorylation; D012313:RNA / Q000378:metabolism; D051381:Rats; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism*; D014227:Triazines / Q000378:metabolism; D014230:Triazoles / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D017362:Cyclic AMP Response Element-Binding Protein; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C047235:N-(1-methyl-2-phenylethyl)adenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D012313:RNA; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000241:Adenosine