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| http://purl.uniprot.org/citations/20562826 | http://www.w3.org/2000/01/rdf-schema#comment | "Prostaglandin E2 (PGE2) is a key mediator of inflammation and contributes to pain hypersensitivity by promoting sensory neurons hyperexcitability. PGE2 synthesis results from activation of a multi-step enzymatic cascade that includes cyclooxygenases (COXs), the main targets of non-steroidal anti-inflammatory drugs (NSAIDs). Although NSAIDs are widely prescribed to reduce inflammatory symptoms such as swelling and pain, associated harmful side effects restrict their long-term use. Therefore, finding new drugs that limit PG production represents an important therapeutic issue. In response to peripheral inflammatory challenges, mice lacking the ATP-gated P2X4 channel (P2X4R) do not develop pain hypersensitivity and show a complete absence of inflammatory PGE2 in tissue exudates. In resting conditions, tissue-resident macrophages constitutively express P2X4R. Stimulating P2X4R in macrophages triggers calcium influx and p38 MAPK phosphorylation, resulting in cytosolic PLA2 (cPLA2) activation and COX-dependent release of PGE2. In naive animals, pain hypersensitivity was elicited by transfer into the paw of ATP-primed macrophages from wild type, but not P2X4R-deficient mice. Thus, P2X4Rs are specifically involved in inflammatory-mediated PGE2 production and might therefore represent useful therapeutic targets."xsd:string |
| http://purl.uniprot.org/citations/20562826 | http://purl.org/dc/terms/identifier | "doi:10.1038/emboj.2010.126"xsd:string |
| http://purl.uniprot.org/citations/20562826 | http://purl.uniprot.org/core/author | "Rassendren F."xsd:string |
| http://purl.uniprot.org/citations/20562826 | http://purl.uniprot.org/core/author | "Ulmann L."xsd:string |
| http://purl.uniprot.org/citations/20562826 | http://purl.uniprot.org/core/author | "Hirbec H."xsd:string |
| http://purl.uniprot.org/citations/20562826 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20562826 | http://purl.uniprot.org/core/name | "EMBO J"xsd:string |
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| http://purl.uniprot.org/citations/20562826 | http://purl.uniprot.org/core/title | "P2X4 receptors mediate PGE2 release by tissue-resident macrophages and initiate inflammatory pain."xsd:string |
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