Differences in the uptake, storage and metabolism of (+)‐ and (—)‐noradrenaline

Abstract

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 (+)-¹⁴C-noradrenaline and (—)-³H-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.