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Pathway Description
Norepinephrine Alpha 1A Adrenergic Blood Vessel Relaxation Action Pathway
Homo sapiens
Drug Action Pathway
Norepinephrine is a sympathomimetic that is regularly found to be the primary neurotransmitter in postganglionic neurons. When taken pharmacologically it acts on the sympathetic nervous system in the heart and the blood vessels. It is mainly used pharmacologically for hypotension and vasodilatory shock states. It acts on all adrenergic receptors, but the main mechanism of action is on the alpha 1A receptor in blood vessel smooth muscles, and the beta 1 receptor in heart muscles.
In the blood vessels, including the aorta, it activates an Alpha adrenergic receptor which activates the Gq protein cascade. This activates Phospolipase C which catalyzes Phosphatidylinositol 4,5-bisphosphate into Inositol 1,4,5-trisphosphate and Diacylglycerol. Diacylglycerol activates protain kinase C which activates the voltage-dependent calcium channel, allowing calcium to enter the cell. Inositol 1,4,5-trisphosphate activates Inositol 1,4,5-trisphosphate receptor on the sarcoplasmic reticulum which also allows calcium to enter the cell from the sarcoplasmic reticulum. This high concentration of calcium in the cytosol attaches to calmodulin which activates Myosin light chain kinase. This enzyme catalyzes Myosin light chain 3 into myosin LC-P which causes myosin to bind to actin and contract the muscle cell. The contraction of this smooth muscle causes the blood vessel to constrict.
References
Norepinephrine Alpha 1A Adrenergic Blood Vessel Relaxation Pathway References
El-Armouche A, Eschenhagen T: Beta-adrenergic stimulation and myocardial function in the failing heart. Heart Fail Rev. 2009 Dec;14(4):225-41. doi: 10.1007/s10741-008-9132-8.
Lachnit WG, Tran AM, Clarke DE, Ford AP: Pharmacological characterization of an alpha 1A-adrenoceptor mediating contractile responses to noradrenaline in isolated caudal artery of rat. Br J Pharmacol. 1997 Mar;120(5):819-26.
Testa R, Guarneri L, Poggesi E, Simonazzi I, Taddei C, Leonardi A: Mediation of noradrenaline-induced contractions of rat aorta by the alpha 1B-adrenoceptor subtype. Br J Pharmacol. 1995 Feb;114(4):745-50.
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