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Noradrenaline (also called norepinephrine) is synthesized in the sympathetic nerves and stored in storage vesicles. When sufficiently stimulated, the vesicles migrate to the end of the nerve and release noradrenaline into the synaptic cleft. As you probably already know, the noradrenaline binds to the adrenergic receptors and stimulates thermogenesis. Next in the chain of events is noradrenaline metabolism, which involves two uptake mechanisms. |
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Noradrenaline MetabolismUptake 1: After stimulating the adrenergic receptors, 85-90% of the noradrenaline is taken back up into the sympathetic nerve (uptake 1) and stored in vesicles or metabolized by monoamine oxidase (specifically, MAO-A) in the mitochondria. The importance of uptake 1 (neuronal uptake) is reflected by the warnings against combining sympathomimetics (ephedrine, phentermine, etc.) with MAO inhibitors -- the risk of overstimulation would be much too high. Uptake 2: Some of the noradrenaline diffuses away from the receptors and is transported by extra-neuronal cells by uptake 2 and metabolized by catechol-O-methyl-transferase (COMT). COMT plays a much smaller role in catecholamine dynamics than MAO. COMT exists in both a soluble and a membrane-bound form. The soluble form of COMT is found in organs and it does not have as high of an affinity for catecholamines as the membrane-bound form.
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1-BK.) Feldman, RS; Meyer, JS, and Quenzer, LF "Principles of Neuropsychopharmacology" Sinauer Associates, Inc. 1997. 2-BK.) Greenspan, FS and Gardner, DG "Basic & Clinical Endocrinology" Lange Medical Books/McGraw-Hill 2000. 3-BK.) Munson, PL; Mueller, RA, and Breese, GR "Principles of Pharmacology. Basic Concepts & Clinical Applications." Chapman & Hall 1996. |
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