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Pathway Description
Vilanterol Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2023-05-19
Last Updated: 2023-10-25
Vilanterol is a long acting beta-2 adrenergic agonist. It can be found under the brand names Anoro, Anoro Ellipta, Breo Ellipta, and Trelegy Ellipta. It has a 24 hour activity and is used as a bronchodilator for the treatment of COPD and asthma. This drug causes the relaxation of bronchial smooth muscle through stimulation of adenylyl cyclase. The result of taking this drug is relaxation of the bronchial smooth muscles causing bronchodilaton and increased airflow. Once vilanterol is administered and it binds to the beta-2 adrenergic receptor, the G protein signalling cascade begins. The alpha and beta/gamma subunits of the G protein separate and GDP is replaced with GTP on the alpha subunit. This alpha subunit then activates adenylyl cyclase which converts ATP to cAMP. cAMP then activates protein kinase A (PKA) which in turn phosphorylates targets and inhibits MLCK through decreased calcium levels causing muscle relaxation. PKA can phosphorylate certain Gq-coupled receptors as well as phospholipase C (PLC) and thereby inhibit G protein-coupled receptor (GPCR) -PLC-mediated phosphoinositide (PI) generation, and thus calcium flux. PKA phosphorylates the inositol 1,4,5-trisphosphate (IP3) receptor to reduce its affinity for IP3 and further limit calcium mobilization. PKA phosphorylates myosin light chain kinase (MLCK) and decreases its affinity to calcium calmodulin, thus reducing activity and myosin light chain (MLC) phosphorylation. PKA also phosphorylates KCa++ channels in ASM, increasing their open-state probability (and therefore K+ efflux) and promoting hyperpolarization. Since myosine light chain kinase is not activated, Serine/threonine-protein phosphatase continues to dephosphorylate myosin LC-P, and more cannot be synthesized so myosin remains unbound from actin causing muscle relaxation. This relaxation of the smooth muscles in the lungs causes the bronchial airways to relax which causes bronchodilation, making it easier to breathe. Some side effects of taking vilanterol may include body aches, chills, cough, fever, and headache.
References
Vilanterol Pathway References
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