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Pathway Description
Epinephrine B2-Adrenergic Bronchodilation Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2021-04-28
Last Updated: 2023-10-25
Epinephrine is a non-selective adrenergic receptor agonist drug used to treat allergic reactions, to restore cardiac rhythm, and to control mucosal congestion, glaucoma, and asthma. It is usually administered intravenously. It targets the bronchiole smooth muscle where it aims to produce relaxation of these muscles to allow for greater airflow into the lungs. Activation of beta-2 adrenergic receptor by Epinephrine activates the Gs signaling pathway. This involves the activation of adenylyl cyclase, which convert ATP to cAMP. This results in high levels of cAMP in the cytosol, which leads to activation of protein kinase A (PKA). For muscle contraction to occur, myosin light chain kinase (MLCK) must phosphorylate myosin light chain. This phosphorylated myosin light chain interacts with actin to produce muscle contraction. MLCK can be activated by a calcium-calmodulin complex. On the other hand, myosin light chain phosphorylase catalyzes the dephosphorylation of the phosphorylated myosin light chain, thus causing relaxation. PKA inactivates the enzyme MLCK, preventing it from phosphorylating myosin light chain. PKA may also perform phosphorylation of intracellular substrates, for example, Gq-coupled receptors, leading to a cascade of intracellular signals which reduce intracellular Ca2+, and therefore reduce activation of the MLCK present in the cytosol. These two mechanisms result in inactivation/reduced activation of MLCK, and as a result, muscle contraction is inhibited and since the dephosphorylated myosin light chain kinase accumulates rather than the phosphorylated myosin light chain kinase, muscle relaxation is enhanced. This allows for greater airflow and is beneficial in conditions like asthma where the individual experiences bronchospasm.
References
Epinephrine B2-Adrenergic Bronchodilation Pathway References
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