Prostaglandin E2 potentiation of P2X3 receptor mediated currents in dorsal root ganglion neurons

Congying Wang, Guang Wen Li, Li-Yen Huang

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Prostaglandin E2 (PGE2) is a well-known inflammatory mediator that enhances the excitability of DRG neurons. Homomeric P2X3 and heteromeric P2X2/3 receptors are abundantly expressed in dorsal root ganglia (DRG) neurons and participate in the transmission of nociceptive signals. The interaction between PGE2 and P2X3 receptors has not been well delineated. We studied the actions of PGE2 on ATP-activated currents in dissociated DRG neurons under voltage-clamp conditions. PGE2 had no effects on P2X2/3 receptor-mediated responses, but significantly potentiated fast-inactivating ATP currents mediated by homomeric P2X3 receptors. PGE2 exerted its action by activating EP3 receptors. To study the mechanism underlying the action of PGE2, we found that the adenylyl cyclase activator, forskolin and the membrane-permeable cAMP analogue, 8-Br-cAMP increased ATP currents, mimicking the effect of PGE2. In addition, forskolin occluded the enhancement produced by PGE2. The protein kinase A (PKA) inhibitors, H89 and PKA-I blocked the PGE2 effect. In contrast, the PKC inhibitor, bisindolymaleimide (Bis) did not change the potentiating action of PGE2. We further showed that PGE2 enhanced α,β-meATP-induced allodynia and hyperalgesia and the enhancement was blocked by H89. These observations suggest that PGE2 binds to EP3 receptors, resulting in the activation of cAMP/PKA signaling pathway and leading to an enhancement of P2X3 homomeric receptor-mediated ATP responses in DRG neurons.

Original languageEnglish (US)
Article number22
JournalMolecular Pain
Volume3
DOIs
StatePublished - Aug 10 2007

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Purinergic P2X3 Receptors
Spinal Ganglia
Dinoprostone
Neurons
Purinergic P2X2 Receptors
Cyclic AMP-Dependent Protein Kinases
Adenosine Triphosphate
Hyperalgesia
Colforsin
Prostaglandin Receptors
Protein Kinase Inhibitors
Adenylyl Cyclases

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Molecular Medicine
  • Cellular and Molecular Neuroscience

Cite this

Prostaglandin E2 potentiation of P2X3 receptor mediated currents in dorsal root ganglion neurons. / Wang, Congying; Li, Guang Wen; Huang, Li-Yen.

In: Molecular Pain, Vol. 3, 22, 10.08.2007.

Research output: Contribution to journalArticle

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