Inflammatory Mediators Potentiate ATP-gated Channels through the P2X 3 Subunit

Martin Paukert, Ralph Osteroth, Hyun Soon Geisler, Uwe Brändle, Elisabeth Glowatzki, J. Peter Ruppersberg, Stefan Gründer

Research output: Contribution to journalArticle

Abstract

The P2X3 receptor is an ATP-gated ion channel predominantly expressed in nociceptive neurons from the dorsal root ganglion. P2X3 receptor channels are highly expressed in sensory neurons and probably contribute to the sensation of pain. Kinetics of P2X3 currents are characterized by rapid desensitization (>100 ms) and slow recovery (>20 s). Thus, any mechanism modulating rate of desensitization and/or recovery may have profound effect on susceptibility of nociceptive neurons expressing P2X3 to ATP. Here we show that currents mediated by P2X3 receptor channels and the heteromeric channel P2X2/3 composed of P2X2 and P2X3 subunits are potentiated by the neuropeptides substance P and bradykinin, which are known to modulate pain perception. The effect is mediated by the respective neuropeptide receptors, can be mimicked by phorbol ester and blocked by inhibitors of protein kinases. Together with data from site-directed mutagenesis our results suggest that inflammatory mediators sensitize nociceptors through phosphorylation of P2X 3 and P2X2/3 ion channels or associated proteins.

Original languageEnglish (US)
Pages (from-to)21077-21082
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number24
DOIs
StatePublished - Jun 15 2001

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Paukert, M., Osteroth, R., Geisler, H. S., Brändle, U., Glowatzki, E., Ruppersberg, J. P., & Gründer, S. (2001). Inflammatory Mediators Potentiate ATP-gated Channels through the P2X 3 Subunit. Journal of Biological Chemistry, 276(24), 21077-21082. https://doi.org/10.1074/jbc.M101465200