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Pathway Description
Isoetharine Action Pathway
Homo sapiens
Drug Action Pathway
Isoetharine is a selective beta-2 adrenergic agonist used as a bronchodilator. This is a fast acting drug offering relief of bronchospasm for the treatment of emphysema, bronchitis, and asthma. Isoetharine is inhaled and acts by activating adenylyl cyclase to increase cAMP levels and subsequently relaxes bronchial smooth muscle. The result of taking this drug is relaxation of the bronchial smooth muscles causing bronchodilaton and increased airflow. Once isoetharine 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. The result of taking this drug is relaxation of the bronchial smooth muscles causing bronchodilaton and increased airflow. Isoetharine has also been shown to stimulate beta-1 receptors in some patients, causing cardiac and CNS side effects. Some side effects of using isoetharine may include dizziness, nervousness, tremor, and headache.
References
Isoetharine Pathway References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Billington CK, Penn RB: Signaling and regulation of G protein-coupled receptors in airway smooth muscle. Respir Res. 2003;4(1):2. Epub 2003 Mar 14.
Pubmed: 12648290
Gomez-Del Rio M, Gerhardt T, Hehre D, Feller R, Bancalari E: Effect of a beta-agonist nebulization on lung function in neonates with increased pulmonary resistance. Pediatr Pulmonol. 1986 Sep-Oct;2(5):287-91. doi: 10.1002/ppul.1950020507.
Pubmed: 2877432
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