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Pathway Description
Ephedrine B2-Adrenergic Vasodilation Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2023-07-17
Last Updated: 2023-11-27
Ephedrine is an alpha and beta-adrenergic agonist indicated to treat hypotension under anesthesia, allergic conditions, bronchial asthma, and nasal congestion. It is administered as an intravenous injection, and can be found under the brand names Akovaz, Bronkaid, Corphedra, Emerphed, Primatene, and Rezipres. Ephedrine increases blood pressure by stimulating heart rate and cardiac output and variably increasing peripheral resistance. It causes bronchodilation due to the activation of beta-adrenergic receptors in the lungs. Ephedrine is a direct and indirect sympathomimetic amine. As a direct effect, ephedrine activates alpha-adrenergic and beta-adrenergic receptors. Ephedrine acts as an agonist of alpha-1, beta-1 and beta-2-adrenergic receptors. The stimulation of alpha-1-adrenergic receptors causes the constriction of veins and a rise in blood pressure, the stimulation of beta-1-adrenergic receptors increases cardiac chronotropy and inotropy, and the stimulation of beta-2-adrenergic receptors causes vasodilation and bronchodilation. At the alpha-1 adrenergic receptor, ephedrine acts as a vasoconstrictor by contracting the smooth muscles. Through the beta-2 adrenergic receptor, the arteries and bronchioles are relaxed through smooth muscle relaxation. Ephedrine 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 smooth muscle relaxation causes the arteries and bronchioles to dilate. Some side effects of using ephedrine may include blurred vision, irregular heartbeat, headache, and tiredness.
References
Ephedrine B2-Adrenergic Vasodilation Pathway References
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