Heterotrimeric G protein signaling: role in asthma and allergic inflammation.
Asthma and rhinitis are pathophysiologic conditions associated with a prototypical allergic response to inhaled allergens consisting of both neuromechanical and inflammatory components. Heptahelical receptors that bind guanosine triphosphate-binding proteins (G proteins), referred to as G protein-coupled receptors (GPCRs), have been intimately linked with asthma and allergic inflammation for many years. G protein signaling mediates responses throughout the immune, nervous, and muscular systems that might contribute to the pathogenesis of allergic processes and asthma. For example, GPCR agonists or antagonists are used as therapies for asthma either by promoting airway smooth muscle relaxation (beta2 adrenergic receptor agonists) or by inhibiting inflammation in the nasal mucosa and airways (cysteinyl leukotriene receptor antagonists). The focus of this review is to explore how downstream signaling cascades elicited by GPCR activation contribute to the allergic phenotype and the mechanism by which pharmaceuticals alter signaling to generate a therapeutic effect. We also discuss physiologic modulators of G protein signaling, such as regulator of G protein signaling proteins and G protein receptor kinases, inasmuch as they represent potential new therapeutic targets in the treatment of atopy and other inflammatory conditions.
Johnson
Eric N
EN
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Druey
Kirk M
KM
D000818:Animals; D001249:Asthma / Q000209:etiology*; D002455:Cell Division; D054774:G-Protein-Coupled Receptor Kinase 5; D020962:Heterotrimeric GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology*; D007249:Inflammation / Q000209:etiology*; D051379:Mice; D009130:Muscle, Smooth / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D020710:RGS Proteins / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology
D020710:RGS Proteins; D011956:Receptors, Cell Surface; D017346:Protein Serine-Threonine Kinases; D054774:G-Protein-Coupled Receptor Kinase 5; C517898:GRK5 protein, human; C517895:Grk5 protein, mouse; D020962:Heterotrimeric GTP-Binding Proteins