UPTAKE, STORAGE AND RELEASE OF H^3--METHYLNOREPINEPHRINE

¹ Department of Pharmacology, University of Göteborg, Göteborg, Sweden

H³--methyl-norepinephrine (H³--Me-NE) is taken up by and stored in sympathetically innervated tissue such as heart and skeletal muscle. The initial uptake of this compound by cardiac muscle appears to be of the same magnitude as that previously reported for H³-norepinephrine and H³-metaraminol. The uptake and subsequent loss of H⁵--Me-NE by skeletal muscle, however, was considerably lower than that found in the heart. This may be due to a lower density of adrenergic innervation or a greater proportion of extracellular binding in skeletal muscle. Unlike norepinephrine, the initial accumulation of -Me-NE in animals pretreated with reserpine is essentially normal. Reserpine partially inhibits the incorporation of H³--Me-NE by subcellular particles and therefore greatly reduces the retention of this amine. The incorporation of some H³--Me-NE into the particulate fraction of cardiac tissue of mice pretreated with high doses of reserpine may be evidence for a reserpine-resistant uptake mechanism in adrenergic granules. Protriptyline, a membrane pump inhibitor, blocks the uptake of H³--methyl-norepinephrine into both heart and skeletal muscle, although the blockade is less complete in the latter tissue. H³--methylnormentanephrine appears to be the principal metabolite of injected H³--Me-NE.