The symptoms of asthma, shortness of breath, chest tightness etc., are caused by narrowing (also known as constriction) of the airways that lead to the lungs and are relieved by drugs (such as beta-agonists) that reverse airway constriction (also known as dilation). Airway constriction and dilation are caused by the airway smooth muscle (ASM) cells contracting and relaxing, processes that are controlled by triggering proteins on the surface of the ASM cells known as G protein–coupled receptors, with the G proteins to which they are coupled determining the intracellular signals initiated. However, the role of Gi proteins in these processes has remained ill-defined

In a study appearing online on April 5 in advance of publication in the May print issue of the Journal of Clinical Investigation, Stephen Liggett and colleagues from the University of Maryland, Baltimore, show that the ASM cells from mice over expressing G-alpha-i2 contracted less than ASM cells from normal mice when stimulated with a chemical that induces asthma-like symptoms, whereas ASM cells from mice expressing a G-alpha-i2 inhibitor contracted more. By contrast, overexpression of G-alpha-i2 decreased airway relaxation by beta-agonists and inhibition of G-alpha-i2 increased the effectiveness of these drugs. This study indicates that Gi proteins have many different roles in regulating airway constriction and dilation, leading the authors to suggest that “pharmacologic or genetic methods to modulate Gi [proteins] could have limited clinical utility.”

TITLE: Crosstalk between Gi and Gq/Gs pathways in airway smooth muscle regulates bronchial contractility and relaxation

AUTHOR CONTACT:
Stephen B. Liggett
University of Maryland School of Medicine, Baltimore, Maryland, USA.
Phone: (410) 706-6256; Fax: (410) 706-6262; E-mail: sligg001@umaryland.edu.

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Contact: Karen Honey
press_releases@the-jci.org
215-573-1850
Journal of Clinical Investigation
5-Apr-2007