Rob Dillard

DocwireNews

Researchers of a new study have identified a novel strategy that isolates the beneficial impact of &beta;2-adrenergic receptor (&beta;2AR) stimulation, a G protein-coupled receptor (GPCR) that rapidly supports airway relaxation and ameliorates asthma symptoms. The results appeared in the journal Molecular Cell.&ldquo;Not only is the &beta;2-adrenergic receptor the mainstay for keeping airways open, it&rsquo;s often studied as a prototype for how GPCRs work, which constitute the targets of 50% of all drugs,&rdquo; explained Jonathan S. Stamler, MD, President, Harrington Discovery Institute at UH, Robert S. and Sylvia K. Reitman Family Foundation Distinguished Professor of Cardiovascular Innovation, and Professor of Medicine and Biochemistry at UH and Case Western Reserve School of Medicine via a <a href="https://www.eurekalert.org/news-releases/962189">press release</a> about the study.All GPCRs, including the &beta;2AR, operate via a feedback loop in which the same molecules that the receptors help generate can circle back and turn the receptors &ldquo;off&rdquo; or inactivate them.In this study, the investigators observed that nitric oxide is a key molecule in the &beta;2AR feedback loop. This finding demonstrates that the production of nitric oxide following &beta;2AR stimulation mediates airway relaxation. However, it shows that overproduction of the molecule also inactivates &beta;2AR, resulting in airway constriction.&ldquo;If you prevent that feedback, you&rsquo;re left with a very powerful airway relaxant that before now had not been thought to be that important in airway relaxation,&rdquo; remarked Dr. Stamler.Moreover, the mice-model study exhibited that mice possessing a particular&nbsp; &beta;2AR genetic mutation receptor are resistant to bronchoconstriction, inflammation, and asthma.&ldquo;Nitric oxide should be thought of as a key new player in how this class of receptors works,&rdquo; Dr. Stamler added. &ldquo;It&rsquo;s responsible for both the beneficial effects of the receptors and for turning them off. And if you can understand how they&rsquo;re being turned off&ndash;how that nitric oxide is popping on to the receptor&ndash;and you can block that, you&rsquo;re going to be left with a new pathway for opening airways. The next step in our research will focus on leveraging this new pathway therapeutically.&rdquo;

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Study Finds New Mechanism of Airway Relaxation in Asthma

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Researchers of a new study have identified a novel strategy that isolates the beneficial impact of β2-adrenergic receptor (β2AR) stimulation, a G protein-coupled receptor ...

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