TY - JOUR
T1 - Inflammatory Mediators Potentiate ATP-gated Channels through the P2X 3 Subunit
AU - Paukert, Martin
AU - Osteroth, Ralph
AU - Geisler, Hyun Soon
AU - Brändle, Uwe
AU - Glowatzki, Elisabeth
AU - Ruppersberg, J. Peter
AU - Gründer, Stefan
PY - 2001/6/15
Y1 - 2001/6/15
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M101465200
DO - 10.1074/jbc.M101465200
M3 - Article
C2 - 11264291
AN - SCOPUS:0035877694
SN - 0021-9258
VL - 276
SP - 21077
EP - 21082
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 24
ER -