RGD Reference Report - Adenosine A(1) and prostaglandin E receptor 3 receptors mediate global airway contraction after local epithelial injury. - Rat Genome Database

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Adenosine A(1) and prostaglandin E receptor 3 receptors mediate global airway contraction after local epithelial injury.

Authors: Zhou, J  Alvarez-Elizondo, MB  Botvinick, E  George, SC 
Citation: Zhou J, etal., Am J Respir Cell Mol Biol. 2013 Mar;48(3):299-305. doi: 10.1165/rcmb.2012-0174OC. Epub 2012 Dec 6.
RGD ID: 10043366
Pubmed: PMID:23221044   (View Abstract at PubMed)
PMCID: PMC3604081   (View Article at PubMed Central)
DOI: DOI:10.1165/rcmb.2012-0174OC   (Journal Full-text)

Epithelial injury and airway hyperresponsiveness are prominent features of asthma. We have previously demonstrated that laser ablation of single epithelial cells immediately induces global airway constriction through Ca(2+)-dependent smooth muscle shortening. The response is mediated by soluble mediators released from wounded single epithelial cells; however, the soluble mediators and signaling mechanisms have not been identified. In this study, we investigated the nature of the epithelial-derived soluble mediators and the associated signaling pathways that lead to the L-type voltage-dependent Ca(2+) channel (VGCC)-mediated Ca(2+) influx. We found that inhibition of adenosine A1 receptors (or removal of adenosine with adenosine deaminase), cyclooxygenase (COX)-2 or prostaglandin E receptor 3 (EP3) receptors, epidermal growth factor receptor (EGFR), or platelet-derived growth factor receptor (PDGFR) all significantly blocked Ca(2+) oscillations in smooth muscle cells and airway contraction induced by local epithelial injury. Using selective agonists to activate the receptors in the presence and absence of selective receptor antagonists, we found that adenosine activated the signaling pathway A1R-->EGFR/PDGFR-->COX-2-->EP3-->VGCCs-->calcium-induced calcium release, leading to intracellular Ca(2+) oscillations in airway smooth muscle cells and airway constriction.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGER3Humanasthma treatmentISOPtger3 (Rattus norvegicus) RGD 
Ptger3Ratasthma treatmentIMP  RGD 
Ptger3Mouseasthma treatmentISOPtger3 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptger3  (prostaglandin E receptor 3)

Genes (Mus musculus)
Ptger3  (prostaglandin E receptor 3 (subtype EP3))

Genes (Homo sapiens)
PTGER3  (prostaglandin E receptor 3)


Additional Information