{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:58:27Z","timestamp":1790499507779,"version":"4.1.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T00:00:00Z","timestamp":1217548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Adenosine (ADO) signaling is altered in both asthma and chronic obstructive pulmonary disease, and the A2B adenosine receptor (A2B-R) may drive pulmonary inflammation. Accordingly, it has been proposed that specific inhibition of the A2B-R could treat inflammatory lung diseases. However, stimulation of the cystic fibrosis transmembrane conductance regulator (CFTR) by ADO may be crucial in permitting the superficial epithelium to maintain airway surface liquid (ASL) volume, which is required to ensure hydrated and clearable mucus. Our goal was to determine which ADO receptor (ADO-R) underlies ASL volume regulation in bronchial epithelia. We used PCR techniques to determine ADO-R expression in bronchial epithelia and used nasal potential difference measurements, Ussing chambers studies, and XZ-confocal microscopy to look at Cl- secretion and ASL volume regulation. The A2B-R was the most highly expressed ADO-R in donor specimens of human bronchial epithelia, and inhibition of ADO-R in vivo prevented activation of CFTR. A2B-R was the only ADO-R detected in cultured human bronchial epithelial cells and inhibition of this receptor with specific A2B-R antagonists resulted in ASL height collapse and a failure to effect ASL height homeostasis. Removal of ADO with ADO deaminase and replacement with 5\u2032N-ethylcarboxamide adenosine resulted in dose-dependent changes in ASL height, and suggested that the cell surface (ADO) may be in excess of 1 \u03bcM, which is sufficient to activate A2B-R. A2B-R are required for ASL volume homeostasis in human airways, and therapies directed at inhibiting A2B-R may lead to a cystic fibrosis\u2013like phenotype with depleted ASL volume and mucus stasis.<\/jats:p>","DOI":"10.1165\/rcmb.2007-0450oc","type":"journal-article","created":{"date-parts":[[2008,3,26]],"date-time":"2008-03-26T21:38:03Z","timestamp":1206567483000},"page":"190-197","source":"Crossref","is-referenced-by-count":49,"title":["A2B Adenosine Receptors Regulate the Mucus Clearance Component of the Lung's Innate Defense System"],"prefix":"10.1093","volume":"39","author":[{"given":"Brett M.","family":"Rollins","sequence":"first","affiliation":[{"name":"Cystic Fibrosis\/Pulmonary Research and Treatment Center, The University of North Carolina, Chapel Hill, North Carolina; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mellisa","family":"Burn","sequence":"additional","affiliation":[{"name":"Pharmacy and Biomolecular Sciences, University of Brighton, 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