METABOLIC REQUIREMENTS FOR THE UPTAKE AND STORAGE OF NOREPINEPHRINE BY THE ISOLATED LEFT ATRIUM OF THE GUINEA PIG

¹ Department of Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, New York

Uptake and retention of norepinephrine (NE) by electrically driven left atria from normal guinea pigs and from reserpine-pretreated guinea pigs, after inhibition of monoamine oxidase (MAO), were not interfered with by inhibition of oxidative metabolism (produced by anoxia or dinitrophenol) or by inhibition of glycolysis (produced by prolonged glucose deprivation or iodoacetate). Normal atria incubated with 5 µg/ml of NE for 5 min and then washed for 40 min actually exhibited a greater net uptake under N2 than under O₂—presumably because NE taken up in excese over that which could be incorporated into neuronal storage granules was protected under N₂ from degradation by MAO. Simultaneous inhibition of oxidative metabolism and glycolysis markedly decreased net uptake in both normal and MAO-inhibited, reserpine-treated atria, and depleted endogenous NE stores in normal atria. Reintroduction of O₂, glucose, or both, to atria which had been subjected to a combination of anoxia and glucose deprivation restored considerably their capacity for uptake of NE. It is concluded that energy derived from metabolism is necessary for the primary step of the uptake process, namely, the inward transport of NE across the cell membrane of the adrenergic nerve terminals, as well as for the subsequent incorporation of NE into intraneuronal storage granules, and that either glycolysis of exogenous glucose or oxidation of noncarbohydrate endogenous substrates can serve as an adequate source of this energy.