| http://purl.uniprot.org/citations/28074005 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28074005 | http://www.w3.org/2000/01/rdf-schema#comment | "Genetic loss of the voltage-gated sodium channel Nav1.7 (Nav1.7-/-) results in lifelong insensitivity to pain in mice and humans. One underlying cause is an increase in the production of endogenous opioids in sensory neurons. We analyzed whether Nav1.7 deficiency altered nociceptive heterotrimeric guanine nucleotide-binding protein-coupled receptor (GPCR) signaling, such as initiated by GPCRs that respond to serotonin (pronociceptive) or opioids (antinociceptive), in sensory neurons. We found that the nociceptive neurons of Nav1.7 knockout (Nav1.7-/-) mice, but not those of Nav1.8 knockout (Nav1.8-/-) mice, exhibited decreased pronociceptive serotonergic signaling through the 5-HT4 receptors, which are Gαs-coupled GPCRs that stimulate the production of cyclic adenosine monophosphate resulting in protein kinase A (PKA) activity, as well as reduced abundance of the RIIβ regulatory subunit of PKA. Simultaneously, the efficacy of antinociceptive opioid signaling mediated by the Gαi-coupled mu opioid receptors was increased. Consequently, opioids inhibited more efficiently tetrodotoxin-resistant sodium currents, which are important for pain-initiating neuronal activity in nociceptive neurons. Thus, Nav1.7 controls the efficacy and balance of GPCR-mediated pro- and antinociceptive intracellular signaling, such that without Nav1.7, the balance is shifted toward antinociception, resulting in lifelong endogenous analgesia."xsd:string |
| http://purl.uniprot.org/citations/28074005 | http://purl.org/dc/terms/identifier | "doi:10.1126/scisignal.aah4874"xsd:string |
| http://purl.uniprot.org/citations/28074005 | http://purl.uniprot.org/core/author | "Sun X."xsd:string |
| http://purl.uniprot.org/citations/28074005 | http://purl.uniprot.org/core/author | "Wood J.N."xsd:string |
| http://purl.uniprot.org/citations/28074005 | http://purl.uniprot.org/core/author | "Hucho T."xsd:string |
| http://purl.uniprot.org/citations/28074005 | http://purl.uniprot.org/core/author | "Isensee J."xsd:string |
| http://purl.uniprot.org/citations/28074005 | http://purl.uniprot.org/core/author | "Moeller K."xsd:string |
| http://purl.uniprot.org/citations/28074005 | http://purl.uniprot.org/core/author | "Pereira V."xsd:string |
| http://purl.uniprot.org/citations/28074005 | http://purl.uniprot.org/core/author | "Emery E."xsd:string |
| http://purl.uniprot.org/citations/28074005 | http://purl.uniprot.org/core/author | "Sexton J.E."xsd:string |
| http://purl.uniprot.org/citations/28074005 | http://purl.uniprot.org/core/author | "Krahe L."xsd:string |
| http://purl.uniprot.org/citations/28074005 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28074005 | http://purl.uniprot.org/core/name | "Sci Signal"xsd:string |
| http://purl.uniprot.org/citations/28074005 | http://purl.uniprot.org/core/pages | "eaah4874"xsd:string |
| http://purl.uniprot.org/citations/28074005 | http://purl.uniprot.org/core/title | "Synergistic regulation of serotonin and opioid signaling contributes to pain insensitivity in Nav1.7 knockout mice."xsd:string |
| http://purl.uniprot.org/citations/28074005 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/28074005 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28074005 |
| http://purl.uniprot.org/citations/28074005 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/28074005 |
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| http://purl.uniprot.org/uniprot/#_A0A0R5RP33-mappedCitation-28074005 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28074005 |
| http://purl.uniprot.org/uniprot/#_A0A0R5RP34-mappedCitation-28074005 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28074005 |
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| http://purl.uniprot.org/uniprot/#_B2RY06-mappedCitation-28074005 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28074005 |