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Updated: Oct 1, 2026

Two-photon Imaging of Microglial Processes' Attraction Toward ATP or Serotonin in Acute Brain Slices
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Two-photon Imaging of Microglial Processes' Attraction Toward ATP or Serotonin in Acute Brain Slices

Published on: January 31, 2019

ADP and AMP induce interleukin-1beta release from microglial cells through activation of ATP-primed P2X7 receptor

Yassar Chakfe1, Rosanne Seguin, Jack P Antel

  • 1Cell Biology of Excitable Tissue Group and Neuroimmunology Unit, Montreal Neurological Institute, Montreal, Quebec, Canada.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|April 12, 2002
PubMed

Insights

Priming P2X(7) receptors with ATP enables subsequent activation by ADP and AMP. This process stimulates interleukin-1beta release from microglia without causing cell death, revealing a novel mechanism for immune cell activation.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • P2X(7) receptors are ATP-gated ion channels crucial in immune cell function.
  • ATP binding to P2X(7) receptors can induce pore formation and cytokine release.

Purpose of the Study:

  • To investigate the effects of endogenous nucleotides on P2X(7) receptors.
  • To understand the role of ATP metabolites in P2X(7) receptor activation and microglial function.

Main Methods:

  • Electrophysiology
  • Fluorescence imaging (YO-PRO-1 dye uptake)
  • Interleukin-1beta release assays
  • Recombinant and primary microglial cell models (mouse and human)

Main Results:

  • ADP and AMP alone do not activate P2X(7) receptors, but sensitize them after ATP priming.
  • ATP-primed P2X(7) receptors respond to ADP and AMP, with sustained signaling after ATP removal.
  • ADP and AMP activate ATP-primed microglia to release interleukin-1beta without inducing cytotoxicity.

Conclusions:

  • P2X(7) receptor activation by ATP metabolites (ADP, AMP) requires prior ATP exposure (priming).
  • This priming mechanism allows for controlled microglial activation and pro-inflammatory cytokine release.
  • P2X(7) receptor sensitization offers a pathway for immune modulation without direct cytotoxicity.

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