Ajay P Nayak1, Dominic Villalba1, Deepak A Deshpande2. 1. Department of Medicine, Center for Translational Medicine and Division of Pulmonary, Allergy and Critical Care Medicine; and Jane & Leonard Korman Respiratory Institute, Thomas Jefferson University, Jefferson Alumni Hall, Room 543, 1020 Locust Street, Philadelphia, PA, 19107, USA. 2. Department of Medicine, Center for Translational Medicine and Division of Pulmonary, Allergy and Critical Care Medicine; and Jane & Leonard Korman Respiratory Institute, Thomas Jefferson University, Jefferson Alumni Hall, Room 543, 1020 Locust Street, Philadelphia, PA, 19107, USA. Deepak.Deshpande@jefferson.edu.
Abstract
PURPOSE OF REVIEW: Asthma is marked by peculiar pathological features involving airway contraction, an impinging inflammation in the lungs, and an inexorably progressive remodeling of pulmonary architecture. Current medications for management of asthma exacerbations fail to optimally mitigate these pathologies, which is partly due to the intrinsic heterogeneity in the development and progression of asthma within different populations. In recent years, the discovery of the ectopic expression of TAS2Rs in extraoral tissues and different cell types, combined with significant strides in gaining mechanistic understanding into receptor signaling and function, has revealed the potential to target TAS2Rs for asthma relief. RECENT FINDINGS: TAS2R activation leads to relaxation of airway smooth muscle cells and bronchodilation. In addition, findings from preclinical studies in murine model of asthma suggest that TAS2R agonists inhibit allergen-induced airway inflammation, remodeling, and hyperresponsiveness. In this review, we expand on the opportunity presented by TAS2Rs in the development of a comprehensive asthma treatment that overcomes the limitations set forth by current asthma therapeutics.
PURPOSE OF REVIEW: Asthma is marked by peculiar pathological features involving airway contraction, an impinging inflammation in the lungs, and an inexorably progressive remodeling of pulmonary architecture. Current medications for management of asthma exacerbations fail to optimally mitigate these pathologies, which is partly due to the intrinsic heterogeneity in the development and progression of asthma within different populations. In recent years, the discovery of the ectopic expression of TAS2Rs in extraoral tissues and different cell types, combined with significant strides in gaining mechanistic understanding into receptor signaling and function, has revealed the potential to target TAS2Rs for asthma relief. RECENT FINDINGS: TAS2R activation leads to relaxation of airway smooth muscle cells and bronchodilation. In addition, findings from preclinical studies in murine model of asthma suggest that TAS2R agonists inhibit allergen-induced airway inflammation, remodeling, and hyperresponsiveness. In this review, we expand on the opportunity presented by TAS2Rs in the development of a comprehensive asthma treatment that overcomes the limitations set forth by current asthma therapeutics.
Authors: S Vincent Wu; Nora Rozengurt; Moon Yang; Steven H Young; James Sinnett-Smith; Enrique Rozengurt Journal: Proc Natl Acad Sci U S A Date: 2002-02-19 Impact factor: 11.205
Authors: Christopher E Brightling; Peter Bradding; Fiona A Symon; Stephen T Holgate; Andrew J Wardlaw; Ian D Pavord Journal: N Engl J Med Date: 2002-05-30 Impact factor: 91.245
Authors: A Ianaro; A Ialenti; P Maffia; L Sautebin; L Rombolà; R Carnuccio; T Iuvone; F D'Acquisto; M Di Rosa Journal: J Pharmacol Exp Ther Date: 2000-01 Impact factor: 4.030
Authors: C L Ordoñez; R Khashayar; H H Wong; R Ferrando; R Wu; D M Hyde; J A Hotchkiss; Y Zhang; A Novikov; G Dolganov; J V Fahy Journal: Am J Respir Crit Care Med Date: 2001-02 Impact factor: 21.405
Authors: Douglas A Kuperman; Xiaozhu Huang; Laura L Koth; Grace H Chang; Gregory M Dolganov; Zhou Zhu; Jack A Elias; Dean Sheppard; David J Erle Journal: Nat Med Date: 2002-07-01 Impact factor: 53.440