CATECHOLAMINE UPTAKE BY SYNAPTOSOMES IN HOMOGENATES OF RAT BRAIN: STEREOSPECIFICITY IN DIFFERENT AREAS

¹ Departments of Pharmacology and Experimental Therapeutics and Psychiatry and the Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland

We have examined the uptake of dl-H³-norepinephrine and H³-dopamine into homogenates from different regions of the rat brain. When the homogenates were centrifuged on continuous sucrose gradients, the H³-amine uptake was localized to fractions that were enriched with synaptosomes. We studied the inhibition of H³-amine uptake into homogenates by d-and l-norepinephrine and d-and l-amphetamine. In the rat cerebral cortex, hypothalamus, medulla oblongata-pons and cerebellum, the K_m for dl-H³-norepinephrine was about 4 x 10^-7 M. In all of these areas, the uptake of norepinephrine was stereospecific with a marked preference for l-norepinephrine; K₁ values for l-norepineplirine were about one-fourth those for d-norepinephrine. The rat corpus striatum, on the other hand, showed no differential preference for d- or l-norepinephrine. Both d- and l-norepinephrine had considerably less affinity than dopamine for the catecholamine transport system in the corpus striatum. Norepinephrine uptake in the cerebral cortex of the monkey and the guinea pig also was stereospecific with K₁ values for l-norepinephrine about one-fourth those for d- norepinephrine. In the rat cerebral cortex, d-amphetamine was 10-fold more potent an inhibitor of dl-H³-norepinephrine uptake than l-amphetamine; however, in the rat corpus striatum, d- and l-amphetamine were equipotent as inhibitors of H³-dopamine uptake.

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