Autoradiographic studies using L-[(14)C]DOPA and L-DOPA reveal regional Na(+)-dependent uptake of the neurotransmitter candidate L-DOPA in the CNS

Neuroscience
Y SugayaY Misu

Abstract

We previously proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a neurotransmitter in the CNS. Receptor and transporter molecules for L-DOPA, however, have not been determined. In the present study, in order to localize the uptake sites of L-DOPA in the CNS, we performed autoradiographic uptake studies using L-[14C]DOPA and L-[3H]DOPA in the uptake study on rat brain slice preparations, and further analyzed the properties of L-DOPA uptake. Image analysis of the L-[14C]DOPA autoradiogram showed a unique heterogeneous distribution of uptake sites in the brain. The intensity was relatively high in the cerebral cortex, the hypothalamus, the cerebellum and the hippocampus, while the density was moderate or even low in the striatum and the substantia nigra. L-DOPA and phenylalanine, but not dopamine (10mM) were able to almost completely inhibit the uptake of L-[14C]DOPA to basal levels. Microautoradiographic studies using L-[3H]DOPA revealed accumulation of dense grains in the median eminence, the supraoptic nucleus of the hypothalamus, the cerebral cortex (layer I) and the hippocampus. In the cerebellum, grains formed in clusters surrounding the Purkinje cells. This grain accumulation was concluded to be in Bergmann glial cells...Continue Reading

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Citations

Feb 1, 2003·Pharmacology & Therapeutics·Yoshimi MisuYoshio Goshima
Jun 27, 2002·Trends in Pharmacological Sciences·Yoshimi MisuTakeaki Miyamae
Feb 27, 2003·Proceedings of the National Academy of Sciences of the United States of America·Carlos A PaladiniRichard D Palmiter
Jun 17, 2003·Journal of Neurochemistry·Regina C C KubruslyFernando G de Mello
Aug 12, 2014·Neuroscience Research·Daiki MasukawaYoshio Goshima
Sep 5, 2014·Journal of Pharmacological Sciences·Yoshio GoshimaMotokazu Koga

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