Stimulatory and inhibitory effects of adenosine A(2A) receptors on nerve growth factor-induced phosphorylation of extracellular regulated kinases 1/2 in PC12 cells

Abstract

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.