Jacqueline Zhou

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 Ca2+ channel -mediated Ca2+ influx.We found that inhibition of adenosine A1 receptors, cyclooxygenase -2 or prostaglandin E receptor 3 receptors, epidermal growth factor receptor, or platelet-derivedgrowthfactor receptor 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 signalingpathwayA1R?EGFR/PDGFR?COX-2?E P3?VGCCs?calciuminduced calcium release, leading to intracellular Ca2+ oscillations in airway smooth muscle cells and airway constriction. © 2013 by the American Thoracic Society.