Elsevier

Neuroscience Letters

Volume 292, Issue 3, 13 October 2000, Pages 183-186
Neuroscience Letters

Stimulatory and inhibitory effects of adenosine A2A receptors on nerve growth factor-induced phosphorylation of extracellular regulated kinases 1/2 in PC12 cells

https://doi.org/10.1016/S0304-3940(00)01461-0Get rights and content

Abstract

Effects of nerve growth factor (NGF), adenosine and an adenosine A2A 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 A2A 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.

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Acknowledgements

We are very grateful to Eva Irenius for her expert technical assistance. We thank Professor Emilio Clementi for the PC12 cells and Janet Holmén for proof reading this manuscript. These studies were supported by the Swedish Medical Research Council (Project No. 2553 and 12707), by Karolinska Institutet and by the Wallenberg Foundation.

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