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Related Experiment Videos

Cytolytic P2X purinoceptors.

F Di Virgilio1, P Chiozzi, S Falzoni

  • 1Department of Experimental and Diagnostic Medicine, Section of General Pathology, University of Ferrara, Italy. fdv@ifeuniv.unife.it

Cell Death and Differentiation
|April 14, 1999
PubMed
Summary

Extracellular ATP (adenosine triphosphate) can kill various cell types by activating purinergic P2X receptors. This cell death mechanism, involving ion imbalance, can lead to necrosis or apoptosis.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Extracellular ATP (adenosine triphosphate) is known to induce cell death in various cell types upon sustained exposure to high concentrations.
  • Purinergic P2X receptors, identified and cloned recently, mediate this ATP-dependent cytotoxicity.
  • P2X receptors exhibit structural similarities to Caenorhabditis elegans degenerins and mammalian amiloride-sensitive Na+ channels (ENaCs).

Purpose of the Study:

  • To summarize the current understanding of P2X receptor-mediated cell death.
  • To explore the mechanisms and pathways involved in ATP-induced cytotoxicity.
  • To discuss the potential physiological roles of P2X receptor activation.

Main Methods:

  • Pharmacological characterization and cloning of P2X receptors.

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  • Analysis of cell death pathways, including ion homeostasis and caspase activation.
  • Review of existing anecdotal and experimental evidence.
  • Main Results:

    • P2X receptor stimulation can induce either necrosis or apoptosis, depending on ATP dose, stimulation duration, and receptor subtype.
    • Perturbation of intracellular ion homeostasis is a critical factor in ATP-dependent cell death.
    • ICE proteases (caspases) are triggered but not essential for this form of cell death.

    Conclusions:

    • The precise physiological role of P2X receptor-mediated cytotoxicity remains unclear.
    • An involvement in immune-mediated reactions is a plausible hypothesis.
    • Further research is needed to fully elucidate the function and implications of P2X receptors in cell death.