The neuroprotective adenosine-activated signal transduction pathway involves activation of phospholipase C

Nucleosides Nucleotides Nucleic Acids. 2006;25(9-11):1283-6. doi: 10.1080/15257770600890939.

Abstract

We have demonstrated before that exposure of neuronal cultures to poisoning by iodoacetic acid (IAA) followed by "reperfusion" (IAA-R insult), results in severe cytotoxicity, which could be markedly attenuated by prior activation of the adenosine A1 receptors. We also have demonstrated that adenosine activates a signal transduction pathway (STP), which involves activation of PKC epsilon and opening of KATP channels. Here, we provide proof for the involvement also of phospholipase C (PLC) in the neuronal protective adenosine-activated STP. R-PIA, a specific A1 adenosine receptor agonist, was found to enhance neuronal PLC activity and protect against the IAA-R insult. The PLC inhibitor U73122, abrogated both R-PIA-induced effects. These results demonstrate that activation of PLC is a vital step in the neuronal protective adenosine-induced STP.

MeSH terms

  • Adenosine / metabolism*
  • Animals
  • Brain / embryology
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Estrenes / pharmacology
  • Iodoacetic Acid / pharmacology
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology
  • Pyrrolidinones / pharmacology
  • Rats
  • Reperfusion Injury
  • Signal Transduction*
  • Type C Phospholipases / metabolism*

Substances

  • Enzyme Inhibitors
  • Estrenes
  • Neuroprotective Agents
  • Pyrrolidinones
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Type C Phospholipases
  • Adenosine
  • Iodoacetic Acid