UPTAKE AND METABOLISM OF dl-NOREPINEPHRINE BY SUBCELLULAR PARTICLES OF RAT HEART

¹ Laboratory of Chemical Pharmacology, National Heart Institute, and Laboratory of Neuroanatomical Sciences, National Institute of Neurological Diseases and Blindness, National Institutes of Health, Bethesda, Maryland

Microsomal fractions prepared from the hearts of rats and mice receiving dl-norepinephrine-7-H³ i.v. were centrifuged through continuous sucrose density gradients. Norepinephrine-containing particles from rat and mouse heart were localized in fractions equivalent in density to 0.55 M sucrose and 0.37 to 0.41 M sucrose, respectively, whereas the bulk of the microsomal constituents had densities equal to or greater than 0.73 M sucrose. Ten to 12% of the norepinephrine originally present in the heart could be accounted for in tile isolated particles. Microsomal particles prepared from sucrose homogenates of rat heart were incubated with dl-norepinephrine-7-H³. At 0°C the particles took up radioactivity to levels approximately twice those in media containing 1 to 96 µmol/ml of amine. At 37°C these ratios increased rapidly to values of 2.6 to 5 but remained little changed thereafter. Much of the radioactivity recovered from particles was accounted for as 3,4-dihydroxyphenylglycolic aldehyde, a product of monoamine oxidase. Uptake of radioactivity by partially purified particles obtained from animals that had received the monoamine oxidase inhibitor, MO-911, did not exceed that in the other microsomal elements from which they had been separated and in most cases was less. Radioactive products other than norepinephrine still accounted for much of the radioactivity taken up.