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dc.contributor.authorCortés-Montero, Elsa
dc.contributor.authorRodríguez-Muñoz, María
dc.contributor.authorRuiz Cantero, María del Carmen 
dc.contributor.authorCobos del Moral, Enrique José 
dc.contributor.authorSánchez-Blázquez, Pilar
dc.contributor.authorGarzón-Niño, Javier
dc.identifier.citationCortés-Montero, E.; Rodríguez-Muñoz, M.; Ruiz-Cantero, M.C.; Cobos, E.J.; Sánchez-Blázquez, P.; Garzón-Niño, J. Calmodulin Supports TRPA1 Channel Association with Opioid Receptors and Glutamate NMDA Receptors in the Nervous Tissue. Int. J. Mol. Sci. 2021, 22, 229. []es_ES
dc.descriptionSupplementary Materials: The following are available online at 7/22/1/229/s1, Figure S1: TRPA1 association with MORs in spinal cord in HINT1-/- and 1R-/- mice. Figure S2: The HINT1 protein or 1R does not support the MOR association with the Nt or Ct regions of TRPA1 channels. Figure S3: CaM mediates the TRPA1 Ct association with MOR in the absence of Ca2+. Figure S4: Pharmacological modulation of TRPA1 associations with MORs and glutamate NMDARs. Figure S5: Formalin-induced inflammatory pain alters TRPA1 associations with MORs and NMDARs. Figure S6: TRPA1 associations with opioid receptors and NMDARs in the CCI model of neuropathic pain.es_ES
dc.descriptionWe would like to thank Gabriela de Alba and María José López for their excellent technical assistancees_ES
dc.description.abstractTransient receptor potential ankyrin member 1 (TRPA1) belongs to the family of thermo TRP cation channels that detect harmful temperatures, acids and numerous chemical pollutants. TRPA1 is expressed in nervous tissue, where it participates in the genesis of nociceptive signals in response to noxious stimuli and mediates mechanical hyperalgesia and allodynia associated with different neuropathies. The glutamate N-methyl-d-aspartate receptor (NMDAR), which plays a relevant role in allodynia to mechanical stimuli, is connected via histidine triad nucleotide-binding protein 1 (HINT1) and type 1 sigma receptor (σ1R) to mu-opioid receptors (MORs), which mediate the most potent pain relief. Notably, neuropathic pain causes a reduction in MOR antinociceptive efficacy, which can be reversed by blocking spinal NMDARs and TRPA1 channels. Thus, we studied whether TRPA1 channels form complexes with MORs and NMDARs that may be implicated in the aforementioned nociceptive signals. Our data suggest that TRPA1 channels functionally associate with MORs, delta opioid receptors and NMDARs in the dorsal root ganglia, the spinal cord and brain areas. These associations were altered in response to pharmacological interventions and the induction of inflammatory and also neuropathic pain. The MOR-TRPA1 and NMDAR-TRPA1 associations do not require HINT1 or σ1R but appear to be mediated by calcium-activated calmodulin. Thus, TRPA1 channels may associate with NMDARs to promote ascending acute and chronic pain signals and to control MOR antinociception.es_ES
dc.description.sponsorshipMICINN Plan Nacional I+D+i RT 2018-093677B-100es_ES
dc.description.sponsorshipUniversity of Granada PPJIB2019.11es_ES
dc.description.sponsorshipMECD FPU 15/02356 FPU16/03213es_ES
dc.rightsAtribución 3.0 España*
dc.subjectTransient receptor potential A1es_ES
dc.subjectMu opioid receptores_ES
dc.subjectGlutamate NMDA receptores_ES
dc.subjectNeuropathic paines_ES
dc.subjectInflammatory paines_ES
dc.titleCalmodulin Supports TRPA1 Channel Association with Opioid Receptors and Glutamate NMDA Receptors in the Nervous Tissuees_ES

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Atribución 3.0 España
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