The constriction and relaxation of the bronchi are key processes that help regulate airflow in the lungs. When smooth muscle contracts, it causes the airways to narrow, restricting the flow of air into the lungs. Conversely, when the smooth muscle relaxes, the airways widen, allowing more air to pass in and out of the lungs. But diseased bronchi are narrowed and obstructed. Therefore, studying the bronchodilation effect of a candidate drug on diseased bronchodilation requires a specific drug treatment as a reference. Creative Biolabs can provide an isoproterenol-induced 3D ex vivo secondary airways (diseased) relaxation model to help customers characterize the therapeutic effect of drug candidates.
Isoproterenol is a synthetic compound that activates β-adrenergic receptors present on the surface of smooth muscle cells in the lungs. Specifically, isoprenaline binding to the β-adrenergic receptors activates the enzyme adenylate cyclase, which converts ATP into cyclic AMP (cAMP). cAMP then activates protein kinase A (PKA), which phosphorylates several downstream targets, including myosin light chain kinase (MLCK), which is responsible for initiating smooth muscle contraction. Phosphorylation of MLCK inhibits its activity, preventing the smooth muscle from contracting and causing bronchoconstriction. Therefore, the isoproterenol-induced 3D ex vivo secondary airways (diseased) relaxation model can be used as an experimental model to study asthma and airway hyperresponsiveness.
Fig.1 Cooperativity of the c-Abl inhibitors and ISO. (Nayak, 2021)
At present, many drugs have been proposed for the treatment of bronchospasm and asthma and have entered the stage of clinical trials. In the stage of verifying the therapeutic effect of candidate drugs in promoting bronchodilation, it is very critical to select an appropriate model that can reflect the clinical therapeutic effect on patients. Creative Biolabs has been working to update the 3D ex vivo human tissue models available to researchers, hoping to provide more recognized models for drug discovery and development. If you need an isoproterenol-induced 3D ex vivo secondary airways (diseased) relaxation model, please contact us and tell us your validation ideas. Of course, we can also provide 3D ex vivo human acetylcholine/carbachol model and 3D ex eivo human COPD model to meet your needs.
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