Regulators of G protein signalling: potential targets for treatment of allergic inflammatory diseases such as asthma.
Asthma, a disease that affects nearly 15% of the world's population, is characterised by lung inflammation and reversible airway obstruction, which leads to wheezing and dyspnoea. Asthma is a prototype for allergic processes initiated by tissue inflammatory leukocytes, such as mast cells, whose secreted mediators recruit lymphocytes and eosinophils to the lung parenchyma. Signals transmitted through G-protein-coupled receptors (GPCRs) contribute to both the development and perpetuation of allergic processes, and pharmacological agents that block or stimulate GPCR action have been a mainstay of allergic disease therapy. Despite the widespread use of GPCR-targeted agents, little is understood about intracellular regulation of G protein pathways in immune cells. Regulators of G protein signalling (RGS proteins) enhance G protein deactivation and may contribute to the specificity and precision characteristic of GPCR signalling pathways. This review discusses the emerging functions of RGS proteins in immune processes and inflammatory states such as asthma, and their potential value as therapeutic targets for the treatment of allergic disease.
Druey
Kirk M
KM
Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 2441 Parklawn Drive, Rockville, MD 20852, USA. kdruey@niaid.nih.gov
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D015195:Drug Design; D020558:GTP Phosphohydrolases / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000502:physiology; D020962:Heterotrimeric GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D005810:Multigene Family; D020710:RGS Proteins / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D018926:Anti-Allergic Agents; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D020710:RGS Proteins; D043562:Receptors, G-Protein-Coupled; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins