Stereoselectivity of catecholamine uptake in noradrenergic and dopaminergic peripheral organs

Abstract

The stereoselectivity of noradrenaline uptake was studied in several adrenergically innervated peripheral organs of the rabbit and rat, as well as in the isolated rabbit retina. (−)- and (+)-noradrenaline bitartrate, and (−)- and (+)-amphetamine surfate, were compared as relative antagonists of the neuronal membrane catecholamine uptake mechanism in the various organs, in order to determine stereoselectivity at both the α and β carbons of noradremaline. It was not possible to demonstrate stereoselectivity unless optimal conditions prevailed. These included the use of finely divided tissues (<0.5 mm on a side), of linear uptake rates, and of non-saturating levels of amines. In the rabbit vas deferens and iris/ciliary, where noradrenaline is the predominant catecholamine and is present in high endogenous concentrations, there was a marked preference for (−)-noradrenaline and for (+)-amphetamine, in contrast with the rabbit retina where dopamine is the chief catecholamine and in which no stereoselectivity was demonstrable. These results confirmed earlier findings in the rat brain in which catecholamine uptake was stereoselective in noradrenergic brain regions but not in the corpus striatum, a dopaminergic region (Coyle and Snyder, 1969). Cardiovascular tissues of the rabbit exhibited a reversal of the usual stereoselectivity, i.e. (+)-noradrenaline had more affinity than (−)-noradrenaline in the rabbit atrium, left ventricle and thoracic aorta, and (−)-amphetamine was more potent an inhibitor of catecholamine uptake than (+)-amphetamine in the thoracic aorta, Amphetamine stereoisomers were equipotent in the tissues of the rabbit heart. Unlike cardiovascular tissues of the rabbit, ventricular slices of the rat displayed a marked preference for (−)-noradrenaline and for (+)-amphetamine.