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Norepinephrine metabolism in rat brain and heart



Norepinephrine metabolism in rat brain and heart



Journal of Pharmacology and Experimental Therapeutics 132: 269-277



Norepinephrine is metabolized largely by catechol-o-methyl transferase (COMT) and monoamine oxidase (MAO). This study evaluates which enzyme is of greater significance in metabolism of norepinephrine in rat brain and heart. MAO activity, in vitro was 3.6 and 5.0 times greater than COMT, in brain and heart, respectively. Rat liver COMT activity is 15 times greater than MAO activity. A significant increase in norepinephrine content was produced by intraperitoneal injection of 4 different MAO inhibitors. Pyrogallol, a COMT inhibitor failed to increase norepinephrine levels even after 18 hours of enzyme inhibition. Norepinephrine was injected intravenously and the rate of disappearance from plasma and heart measured. Animals pretreated with iproniazid showed a marked accumulation in the myocardium relative to the plasma. Pyrogallol pretreated produced a prolonged plasma clearance but no accumulation in the heart. These experiments show that endogenous norepinephrine accumulates in the brain and heart when an MAO inhibitor is present. Exogenous norepinephrine accumulates in the heart under the same conditions. Neither effect is produced by a COMT inhibitor. Results suggest that oxidative deamination is the more significant metabolic pathway in the brain and heart of the rat.

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Accession: 025089354

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PMID: 13696647



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