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ATP and UTP excite sensory neurons and induce CREB phosphorylation through the metabotropic receptor, P2Y2

Derek C Molliver1, Sean P Cook, Julie A Carlsten

  • 1Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA.

The European Journal of Neuroscience
|November 28, 2002
PubMed

Insights

Extracellular ATP and UTP activate sensory neurons via P2Y2 receptors, leading to CREB phosphorylation and sustained firing. This suggests P2Y2 receptors regulate nociceptor responses and phenotype.

Area of Science:

  • Neuroscience
  • Cellular Signaling
  • Sensory Biology

Background:

  • Extracellular ATP rapidly excites nociceptive sensory neurons via P2X receptors.
  • The role of other ATP receptors in sustained sensory neuron responses is less understood.

Purpose of the Study:

  • To investigate the slow, sustained actions of extracellular nucleotides on rat sensory neurons.
  • To identify the specific receptors mediating these sustained responses.

Main Methods:

  • Patch-clamp electrophysiology to record action potentials.
  • Western blotting to detect CREB phosphorylation.
  • In situ hybridization to analyze P2Y2 receptor mRNA expression.

Main Results:

  • ATP and UTP induced slow, sustained action potential firing and CREB phosphorylation in sensory neurons.
  • These effects were mediated by the metabotropic P2Y2 receptor, not ionotropic P2X receptors.
  • P2Y2 receptor mRNA was widely expressed in sensory neurons, particularly in small, peripherin-positive neurons.

Conclusions:

  • The P2Y2 receptor contributes to ATP-mediated sensory signaling transduction.
  • P2Y2 receptor activation influences sustained nociceptor activity and may regulate nociceptor phenotype.
  • These findings highlight a novel role for P2Y2 receptors in pain signaling.

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