title: Evaluation of Mucociliary Clearance by Three Dimension Micro-CT-SPECT in Guinea Pig: Role of Bitter Taste Agonists.
abstract: Different image techniques have been used to analyze mucociliary clearance (MCC) in humans, but current small animal MCC analysis using in vivo imaging has not been well defined. Bitter taste receptor (T2R) agonists increase ciliary beat frequency (CBF) and cause bronchodilation but their effects in vivo are not well understood. This work analyzes in vivo nasal and bronchial MCC in guinea pig animals using three dimension (3D) micro-CT-SPECT images and evaluates the effect of T2R agonists. Intranasal macroaggreggates of albumin-Technetium 99 metastable (MAA-Tc99m) and lung nebulized Tc99m albumin nanocolloids were used to analyze the effect of T2R agonists on nasal and bronchial MCC respectively, using 3D micro-CT-SPECT in guinea pig. MAA-Tc99m showed a nasal mucociliary transport rate of 0.36 mm/min that was increased in presence of T2R agonist to 0.66 mm/min. Tc99m albumin nanocolloids were homogeneously distributed in the lung of guinea pig and cleared with time-dependence through the bronchi and trachea of guinea pig. T2R agonist increased bronchial MCC of Tc99m albumin nanocolloids. T2R agonists increased CBF in human nasal ciliated cells in vitro and induced bronchodilation in human bronchi ex vivo. In summary, T2R agonists increase MCC in vivo as assessed by 3D micro-CT-SPECT analysis.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Ortiz
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Ortiz
authors.affiliation: Jaume I University, faculty of Medicine, Castellón, Spain.|Department of Pharmacy, University General Hospital Consortium, Valencia, Spain.|CIBERES, Health Institute Carlos III, Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Milara
authors.affiliation: Rhinology Unit, University General Hospital Consortium, Valencia, Spain.|Department of Surgery, Faculty of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Armengot
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Valencia, Valencia, Spain.|Jaume I University, faculty of Medicine, Castellón, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Sanz
authors.affiliation: Pathological Anatomy Department, Hospital Clínico Universitario of Valencia, Valencia, Spain.
authors.forename: Desamparados
authors.initials: D
authors.lastname: Compañ
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Valencia, Valencia, Spain.|CIBERES, Health Institute Carlos III, Valencia, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Morcillo
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Valencia, Valencia, Spain.|CIBERES, Health Institute Carlos III, Valencia, Spain.|Teaching and Research Unit, University General Hospital Consortium, Valencia, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Cortijo
mesh_terms: D000418:Albumins / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D006168:Guinea Pigs; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging; D009079:Mucociliary Clearance / Q000187:drug effects / Q000502:physiology*; D053758:Nanoparticles; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D000072098:Single Photon Emission Computed Tomography Computed Tomography / Q000379:methods*; D055114:X-Ray Microtomography / Q000379:methods*
chemical_list: D000418:Albumins; D043562:Receptors, G-Protein-Coupled