Adenosine A1 and prostaglandin E receptor 3 receptors mediate global airway contraction after local epithelial injury

Jian Zhou, Martha B. Alvarez-Elizondo, Elliot Botvinick, Steven George

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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 (VGCC)-mediated Ca2+ influx.We found that inhibition of adenosine A1 receptors (or removal of adenosine with adenosine deaminase), cyclooxygenase (COX)-2 or prostaglandin E receptor 3 (E P3) receptors, epidermal growth factor receptor (EGFR), or platelet-derivedgrowthfactor 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 signalingpathwayA1R?EGFR/PDGFR?COX-2?E P3?VGCCs?calciuminduced calcium release, leading to intracellular Ca2+ oscillations in airway smooth muscle cells and airway constriction.

Original languageEnglish (US)
Pages (from-to)299-305
Number of pages7
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume48
Issue number3
DOIs
StatePublished - Mar 1 2013

Keywords

  • ATP
  • Cyclooxygenase-2
  • Epidermal growth factor receptor
  • L-type voltage-dependent Ca channels
  • Platelet-derived growth factor receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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