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Feb 12, 2009
 |  BC Innovations  |  Targets & Mechanisms

New shock treatment

German researchers have found that targeting two G proteins could treat the vascular symptoms of anaphylactic shock while avoiding the cardiovascular side effects of epinephrine, the standard of care. If a selective inhibitor for the two proteins, GNAQ and GNA11, proves safer than epinephrine, the finding could result in the first new treatment for anaphylaxis in more than six decades.

Anaphylaxis is a severe, systemic allergic reaction characterized by a decrease in blood pressure due to blood vessel dilation, an increase in vascular permeability that can lead to angioedema, and constriction of airway passages, among other symptoms.

Epinephrine addresses the two main ways anaphylaxis becomes lethal: it reverses vascular permeability and opens the airways. But epinephrine is associated with serious cardiovascular side effects, including tachycardia and arrhythmia, which can be fatal in anaphylactic patients with hypertension or coronary artery disease (CAD).

Allergens trigger anaphylaxis by stimulating the release of histamine, platelet-activating factor (PAF) and other proinflammatory molecules into the bloodstream. These molecules are thought to activate G proteins on endothelial cells of the heart, blood vessels and airways. But which G proteins are involved has not been clear, due in part to the lack of mouse models that would allow the function of different members of the family of signal transducers to be examined separately.

The German group now has developed a mouse model, which they described in a paper in the Journal of Experimental Medicine.1 In mice whose endothelial cells were deficient in different G proteins, the researchers found that two of the proteins appeared to be involved in anaphylaxis: G protein q polypeptide (GNAQ; Gaq) and G protein a11 (Gq class) (GNA11). Similar results were seen in human endothelial cells.

Next, the team generated mice with...

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