The contribution of transient receptor potential ankyrin 1 (TRPA1) to the in vivo nociceptive effects of prostaglandin E2

Dall'Acqua, M.; Bonet, Ivan José Magayewski; Zampronio, Aleksander Roberto; Tambeli, Cláudia Herrera; Parada, Carlos Amílcar; Fischer, Luana

doi:10.1016/j.lfs.2014.02.031

Cited by 29 publications

(21 citation statements)

References 29 publications

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“…PGE2 is known to modulate TRPA1 function both in vitro and in vivo [30,31]. Therefore, it can be hypothesized that OxPAPC acts through EP2 or DP receptors to activate TRPA1 indirectly.…”

Section: Resultsmentioning

confidence: 99%

Oxidized Phospholipid OxPAPC Activates TRPA1 and Contributes to Chronic Inflammatory Pain in Mice

et al. 2016

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Oxidation products of the naturally occurring phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycerol-3-phosphatidylcholine (PAPC), which are known as OxPAPC, accumulate in atherosclerotic lesions and at other sites of inflammation in conditions such as septic inflammation and acute lung injury to exert pro- or anti-inflammatory effects. It is currently unknown whether OxPAPC also contributes to inflammatory pain and peripheral neuronal excitability in these conditions. Here, we observed that OxPAPC dose-dependently and selectively activated human TRPA1 nociceptive ion channels expressed in HEK293 cells in vitro, without any effect on other TRP channels, including TRPV1, TRPV4 and TRPM8. OxPAPC agonist activity was dependent on essential cysteine and lysine residues within the N-terminus of the TRPA1 channel protein. OxPAPC activated calcium influx into a subset of mouse sensory neurons which were also sensitive to the TRPA1 agonist mustard oil. Neuronal OxPAPC responses were largely abolished in neurons isolated from TRPA1-deficient mice. Intraplantar injection of OxPAPC into the mouse hind paw induced acute pain and persistent mechanical hyperalgesia and this effect was attenuated by the TRPA1 inhibitor, HC-030031. More importantly, we found levels of OxPAPC to be significantly increased in inflamed tissue in a mouse model of chronic inflammatory pain, identified by the binding of an OxPAPC-specific antibody. These findings suggest that TRPA1 is a molecular target for OxPAPC and OxPAPC may contribute to chronic inflammatory pain through TRPA1 activation. Targeting against OxPAPC and TRPA1 signaling pathway may be promising in inflammatory pain treatment.

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“…PGE2 is known to modulate TRPA1 function both in vitro and in vivo [30,31]. Therefore, it can be hypothesized that OxPAPC acts through EP2 or DP receptors to activate TRPA1 indirectly.…”

Section: Resultsmentioning

confidence: 99%

Oxidized Phospholipid OxPAPC Activates TRPA1 and Contributes to Chronic Inflammatory Pain in Mice

et al. 2016

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“…Such model systems would prevent PKA- and/or PKC-mediated sensitization, provided the lack of equally-expressed AKAP, as afforded by results demonstrated here in. Indeed, TRPA1 sensitization in more physiologically-relevant cell models demonstrate sensitivity to protein kinase manipulation 71, 72 .…”

Section: Discussionmentioning

confidence: 99%

A-Kinase Anchoring Protein 79/150 Scaffolds Transient Receptor Potential A 1 Phosphorylation and Sensitization by Metabotropic Glutamate Receptor Activation

Brackley

Gomez

Guerrero

et al. 2017

Sci Rep

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Mechanical pain serves as a base clinical symptom for many of the world’s most debilitating syndromes. Ion channels expressed by peripheral sensory neurons largely contribute to mechanical hypersensitivity. Transient Receptor Potential A 1 (TRPA1) is a ligand-gated ion channel that contributes to inflammatory mechanical hypersensitivity, yet little is known as to the post-translational mechanism behind its somatosensitization. Here, we utilize biochemical, electrophysiological, and behavioral measures to demonstrate that metabotropic glutamate receptor-induced sensitization of TRPA1 nociceptors stimulates targeted modification of the receptor. Type 1 mGluR5 activation increases TRPA1 receptor agonist sensitivity in an AKA-dependent manner. As a scaffolding protein for Protein Kinases A and C (PKA and PKC, respectively), AKAP facilitates phosphorylation and sensitization of TRPA1 in ex vivo sensory neuronal preparations. Furthermore, hyperalgesic priming of mechanical hypersensitivity requires both TRPA1 and AKAP. Collectively, these results identify a novel AKAP-mediated biochemical mechanism that increases TRPA1 sensitivity in peripheral sensory neurons, and likely contributes to persistent mechanical hypersensitivity.

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“…BK and PGE2), leading to pain hypersensitivity. Similar to TRPV1, TRPA1 can be potentiated by BK and PGE2, 112,113 which activates Gq and Gs-coupled GPCR, respectively, resulting in the activation of phospholipase C (PLC) and PKA. Blocking PLC and PKA prevented the sensitization of TRPA1 induced by BK, 112 and activation of PLC and PKA evoked TRPA1-mediated hyperalgesia.…”

Section: Modulation Of Trpa1mentioning

confidence: 99%

“…Blocking PLC and PKA prevented the sensitization of TRPA1 induced by BK, 112 and activation of PLC and PKA evoked TRPA1-mediated hyperalgesia. 113 Mechanistically, activation of PLC/PKA pathways enhanced trafficking of TRPA1 to the cell membrane, 114 suggesting that the PLC and PKA pathways potentiates TRPA1 by promoting forward trafficking of the channel. Interestingly, several downstream signaling messengers of the Gq-PLC pathway such as Ca 2C , diacylglycerol (DAG) and arachidonic acid (AA) can directly activate TRPA1, [115][116][117] and was suggested to be a mechanism underlying BK-elicited excitation of sensory neurons and pain.…”

Section: Modulation Of Trpa1mentioning

confidence: 99%

Molecular sensors and modulators of thermoreception

Zhang

2015

Channels

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The contribution of transient receptor potential ankyrin 1 (TRPA1) to the in vivo nociceptive effects of prostaglandin E2

Cited by 29 publications

References 29 publications

Oxidized Phospholipid OxPAPC Activates TRPA1 and Contributes to Chronic Inflammatory Pain in Mice

Oxidized Phospholipid OxPAPC Activates TRPA1 and Contributes to Chronic Inflammatory Pain in Mice

A-Kinase Anchoring Protein 79/150 Scaffolds Transient Receptor Potential A 1 Phosphorylation and Sensitization by Metabotropic Glutamate Receptor Activation

Molecular sensors and modulators of thermoreception

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