Stimulatory and inhibitory effects of adenosine A(2A) receptors on nerve growth factor-induced phosphorylation of extracellular regulated kinases 1/2 in PC12 cells.
Effects of nerve growth factor (NGF), adenosine and an adenosine A(2A) receptor agonist (CGS 21680) on the phosphorylation of extracellular-regulated kinases 1/2 (ERK1/2) were examined in PC12 cells. Adenosine and CGS 21680stimulated ERK1/2, but inhibited the phosphorylation of ERK1/2 induced by a 10 min incubation with NGF. Longer treatment with CGS 21680 and NGF (1-2h) resulted in an additive effect on the activation of ERK1/2. Forskolin exerted the same effects, suggesting that they are mediated by cyclic AMP. These results indicate that adenosine A(2A) receptor induced increases in cyclic AMP can stimulate ERK1/2 phosphorylation per se, inhibit the initial and enhance the late NGF-induced activation of ERK1/2. These results may be explained by the fact that NGF action is mediated via different pathways at early and late time points.
Arslan
G
G
Department of Physiology and Pharmacology, Section of Molecular Neuropharmacology, Karolinska Institute, S-171 77, Stockholm, Sweden. giulia.arslan@fyfa.ki.se
Fredholm
B B
BB
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004357:Drug Synergism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D016716:PC12 Cells; D010627:Phenethylamines / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D005576:Colforsin; D020932:Nerve Growth Factor; D000242:Cyclic AMP; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D000241:Adenosine