Differences in the uptake, storage and metabolism of (+)- and (-)-noradrenaline.
1. The rate of uptake of (+)- and (-)-noradrenaline was measured in isolated perfused hearts of reserpine treated rats, mice and guinea-pigs by fluorimetric analysis of the removal of catecholamine from the perfusion medium. In rat and mouse heart (-)-noradrenaline was taken up significantly more rapidly than (+)-noradrenaline, but no stereochemical specificity was found for noradrenaline uptake in guinea-pig hearts.2. Using radioactively labelled (+)-(14)C-noradrenaline and (-)-(3)H-noradrenaline, the kinetic constants for uptake into noradrenaline-containing and dopamine-containing synaptosomes from rat brain were determined. The uptake by noradrenaline terminals in the hypothalamus had a higher affinity for (-)-noradrenaline than for the (+)-isomer, but no differences in affinity were found for uptake into dopamine terminals.3. When equal amounts of labelled (+)- and (-)-noradrenaline were injected in vivo in double isotope experiments, the (+)-isomer disappeared more rapidly than the (-)-isomer from rat heart and spleen, but no significant differences were found between the rates of disappearance of the two isomers from rat brain or in the whole mouse.4. Analysis of the radioactive metabolites of the two isomers of noradrenaline after administration of mixed doses of the labelled substances showed that a significantly higher proportion of (+)-noradrenaline was metabolized to normetanephrine than of (-)-noradrenaline, in the whole mouse, rat heart and rat brain.
D000818:Animals; D001921:Brain / Q000378:metabolism; D002247:Carbon Isotopes; D005470:Fluorometry; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007031:Hypothalamus / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D009647:Normetanephrine / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D013045:Species Specificity; D013154:Spleen / Q000378:metabolism; D013237:Stereoisomerism; D013574:Synaptosomes / Q000378:metabolism; D014020:Tissue Extracts / Q000378:metabolism; D014316:Tritium
D002247:Carbon Isotopes; D014020:Tissue Extracts; D009647:Normetanephrine; D014316:Tritium; D012110:Reserpine; D009638:Norepinephrine