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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.
Pubmed: (View Article at PubMed) PMID:23221044
DOI: Full-text: DOI:10.1165/rcmb.2012-0174OC

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.

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CRRD Object Information
CRRD ID: 10043366
Created: 2015-05-26
Species: All species
Last Modified: 2015-05-26
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.