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

Laryngoscope. 2013 Feb;123(2):306-10. doi: 10.1002/lary.23586. Epub 2012 Sep 10.

Abstract

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 (A(2A)(-/-), A(2B)(-/-), A(2A)(-/-)A(2B)(-/-), and A(1)(-/- )A(3)(-/-)) mice.

Results: Exogenous adenosine aerosol robustly enhanced nasal MCC. The augmentation of MCC by adenosine was abolished in mice lacking both A(2A) and A(2B) receptors, but remained robust in mice lacking either A(2A) or A(2B) . Likewise, basal nasal MCC was reduced in mice lacking both the A(2A) and A(2B) receptors, but was statistically identical among wild-type mice and mice lacking either A(2A) or A(2B) .

Conclusions: These findings indicate that activation of both G(s) -coupled adenosine receptors can accelerate nasal MCC. Targeting these receptors may represent a novel therapeutic approach for enhancing MCC in CRS.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine / administration & dosage
  • Adenosine / pharmacology*
  • Administration, Intranasal
  • Aerosols
  • Analysis of Variance
  • Animals
  • Female
  • Gamma Cameras
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Mucociliary Clearance / drug effects*
  • Prospective Studies
  • Receptor, Adenosine A2A / drug effects*
  • Receptor, Adenosine A2B / drug effects*
  • Technetium Tc 99m Sulfur Colloid

Substances

  • Aerosols
  • Receptor, Adenosine A2A
  • Receptor, Adenosine A2B
  • Technetium Tc 99m Sulfur Colloid
  • Adenosine