Adenosine increases nasal mucociliary clearance rate in mice through A2A and A2B adenosine receptors

Objectives/Hypothesis: Mucociliary clearance (MCC) is an important mechanism of host defense in the upper and lower respiratory tract. Impaired MCC plays a critical role in the development and perpetuation of chronic rhinosinusitis (CRS). The aim of this investigation was to determine the influence of adenosine on nasal MCC, and to determine the receptors mediating this physiology in vivo. Study Design: Prospective study using an animal model. Methods: Nasal MCC was measured by whole-nose scintigraphic acquisition in vivo. The effects of both endogenous and exogenous adenosine were investigated in wild-type and adenosine receptor knockout (A2A/, A2B/, A2A/A2B/, and A1/ A3/) mice. Results: Exogenous adenosine aerosol robustly enhanced nasal MCC. The augmentation of MCC by adenosine was abolished in mice lacking both A2A and A2B receptors, but remained robust in mice lacking either A2A or A2B. Likewise, basal nasal MCC was reduced in mice lacking both the A2A and A2B receptors, but was statistically identical among wild-type mice and mice lacking either A2A or A2B. Conclusions: These findings indicate that activation of both Gs-coupled adenosine receptors can accelerate nasal MCC. Targeting these receptors may represent a novel therapeutic approach for enhancing MCC in CRS. Laryngoscope, 2012