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

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.

• Authors: A Rogel, Y Bromberg, O Sperling, E Zoref-Shani
• Journal: Nucleosides, nucleotides & nucleic acids (Nucleosides Nucleotides Nucleic Acids) Vol. 25 Issue 9-11 Pg. 1283-6 ( 2006) ISSN: 1525-7770 [Print] United States
• PMID: 17065107 (Publication Type: Journal Article)

Chemical References

• 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

Topics

• 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)