Up-regulation of P2X2, P2X4 receptor and ischemic cell death: prevention by P2 antagonists

F Cavaliere1, F Florenzano, S Amadio

  • 1IRCCS Santa Lucia Foundation, Rome, Italy.

Neuroscience
|July 10, 2003
PubMed

Insights

Selected P2X receptors (P2X2 and P2X4) are upregulated during glucose/oxygen deprivation, contributing to neuronal cell death. Antagonists of these receptors show neuroprotective potential against ischemic injury.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Pharmacology

Background:

  • Extracellular ATP acting on P2X receptors is implicated in neuronal injury.
  • Glucose/oxygen deprivation triggers cell death pathways in the central nervous system.

Purpose of the Study:

  • To investigate the role of specific P2X receptors in neuronal cell death induced by metabolic impairment.
  • To evaluate the neuroprotective effects of P2 receptor antagonists in vitro and in vivo.

Main Methods:

  • Organotypic cultures from hippocampus, cortex, and striatum were subjected to glucose/oxygen deprivation.
  • In vivo studies involved gerbils undergoing bilateral common carotid occlusion.
  • Expression levels of P2X2 and P2X4 receptors were analyzed using immunofluorescence.
  • The effects of P2 receptor antagonists (Resiniferatoxin and Suramin) were assessed.

Main Results:

  • Glucose/oxygen deprivation upregulated P2X2 and P2X4 receptors in hippocampal cultures.
  • Ischemic conditions caused neuronal loss in hippocampal, cortical, and striatal cultures.
  • Resiniferatoxin and Suramin prevented these detrimental effects in vitro.
  • In vivo, P2X2 and P2X4 receptors were upregulated in the hippocampus following ischemic injury.
  • P2X2 was found in neurons, while P2X4 was localized to microglia in the affected areas.

Conclusions:

  • P2X2 and P2X4 receptors are directly involved in neuronal death caused by metabolic impairment.
  • P2 receptor antagonists demonstrate potential as neuroprotective agents against ischemic brain damage.

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