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

Neurosci Lett. 2000 Oct 13;292(3):183-6. doi: 10.1016/s0304-3940(00)01461-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • Adenosine / pharmacology
  • Animals
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • Drug Synergism
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism*
  • Nerve Growth Factor / metabolism*
  • Nerve Growth Factor / pharmacology
  • PC12 Cells
  • Phenethylamines / pharmacology
  • Phosphorylation / drug effects
  • Purinergic P1 Receptor Agonists
  • Rats
  • Receptor, Adenosine A2A
  • Receptors, Purinergic P1 / metabolism*
  • Signal Transduction / drug effects


  • Phenethylamines
  • Purinergic P1 Receptor Agonists
  • Receptor, Adenosine A2A
  • Receptors, Purinergic P1
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • Colforsin
  • Nerve Growth Factor
  • Cyclic AMP
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Adenosine