TY - JOUR
T1 - Stereoselectivity of catecholamine uptake in noradrenergic and dopaminergic peripheral organs
AU - Hendley, Edith D.
AU - Snyder, Solomon H.
PY - 1972/7
Y1 - 1972/7
N2 - 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.
AB - 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.
KW - Amphetamine Dopamine
KW - Atrium
KW - Catecholamine
KW - Noradrenaline
KW - Reserpine
KW - Retina
KW - Vas deferens
KW - Ventricle
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U2 - 10.1016/0014-2999(72)90077-5
DO - 10.1016/0014-2999(72)90077-5
M3 - Article
C2 - 5065531
AN - SCOPUS:0015367080
SN - 0014-2999
VL - 19
SP - 56
EP - 66
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -