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.
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.
Authors: Thiago Inácio Teixeira do Carmo; Victor Emanuel Miranda Soares; Jonatha Wruck; Fernanda Dos Anjos; Débora Tavares de Resende E Silva; Sarah Franco Vieira de Oliveira Maciel; Margarete Dulce Bagatini Journal: Inflamm Res Date: 2021-04-27 Impact factor: 4.575
Authors: Adam J Kimple; Alaina L Garland; Staci P Cohen; Vincent Setola; Francis S Willard; Thomas Zielinski; Robert G Lowery; Robert Tarran; David P Siderovski Journal: Laryngoscope Date: 2013-10-02 Impact factor: 3.325