Bronchoprotection and bronchorelaxation in asthma: New targets, and new ways to target the old ones.
Despite over 50years of inhaled beta-agonists and corticosteroids as the default management or rescue drugs for asthma, recent research suggests that new therapeutic options are likely to emerge. This belief stems from both an improved understanding of what causes and regulates airway smooth muscle (ASM) contraction, and the identification of new targets whose inhibition or activation can relax ASM. In this review we discuss the recent findings that provide new insight into ASM contractile regulation, a revolution in pharmacology that identifies new ways to "tune" G protein-coupled receptors to improve therapeutic efficacy, and the discovery of several novel targets/approaches capable of effecting bronchoprotection or bronchodilation.
Center for Translational Medicine and Jane and Leonard Korman Lung Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States. Electronic address: tonio.pera@jefferson.edu.
Tonio
T
Pera
Center for Translational Medicine and Jane and Leonard Korman Lung Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States. Electronic address: raymond.penn@jefferson.edu.
Raymond B
RB
Penn
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D018118:Chloride Channels / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism; D018077:Receptors, Leukotriene / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D054460:rho-Associated Kinases / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D018118:Chloride Channels; D010726:Phosphodiesterase Inhibitors; D044464:Receptor, PAR-2; D044169:Receptors, Calcium-Sensing; D043562:Receptors, G-Protein-Coupled; D018079:Receptors, GABA; D018077:Receptors, Leukotriene; D018078:Receptors, Prostaglandin E; D054460:rho-Associated Kinases; C083169:leukotriene D4 receptor
Airway smooth muscle; Asthma; Biased agonism; Bronchodilation; GPCR; Inhaled corticosteroids