Stimulatory and inhibitory effects of adenosine A2A 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 ASA receptor agonist (CGS 21680) on the phosphorylation of extracellular-regulated kinases 1/2 (ERK1/2) were examined in PC12 cells. Adenosine and CGS 21680 stimulated ERK1/2, but inhibited the phosphorylation of ERK1/2 induced by a 10 min incubation with NGF. Longer treatment with CGS 21680 and NGF (1-2 h) 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 ASA 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. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.