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Titolo:
Autoradiographic studies using L-[C-14]DOPA and L-[H-3]DOPA reveal regional NA(+)-dependent uptake of the neurotransmitter candidate L-DOPA in the CNS
Autore:
Sugaya, Y; Sasaki, Y; Goshima, Y; Kitahama, K; Kusakabe, T; Miyamae, T; Kato, T; Misu, Y;
Indirizzi:
Yokohama City Univ, Sch Med, Dept Pharmacol, Yokohama, Kanagawa 2360004, Japan Yokohama City Univ Yokohama Kanagawa Japan 2360004 anagawa 2360004, Japan Yokohama City Univ, Sch Med, Dept Anat, Yokohama, Kanagawa 2360004, Japan Yokohama City Univ Yokohama Kanagawa Japan 2360004 anagawa 2360004, Japan Fac Med, INSERM U480, Dept Expt Med, F-69373 Lyon, France Fac Med Lyon France F-69373 RM U480, Dept Expt Med, F-69373 Lyon, France Yokohama City Univ, Lab Mol Recognit, Grad Sch Integrated Sci, Yokohama, Kanagawa 2360027, Japan Yokohama City Univ Yokohama Kanagawa Japan 2360027 anagawa 2360027, Japan
Titolo Testata:
NEUROSCIENCE
fascicolo: 1, volume: 104, anno: 2001,
pagine: 1 - 14
SICI:
0306-4522(2001)104:1<1:ASULAL>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSPORTER MESSENGER-RNA; AMINO-ACID DECARBOXYLASE; RAT HYPOTHALAMIC SLICES; HORMONE-RELEASING FACTOR; ENDOGENOUS L-DOPA; IMMUNOCYTOCHEMICAL LOCALIZATION; COMPETITIVE ANTAGONIST; IMMUNOREACTIVE NEURONS; VENTROLATERAL MEDULLA; MIDBRAIN NEURONS;
Keywords:
L-DOPA; neurotransmitter; uptake; transporter; autoradiography; rat brain slice;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Goshima, Y Yokohama City Univ, Sch Med, Dept Pharmacol, Yokohama, Kanagawa2360004, Japan Yokohama City Univ Yokohama Kanagawa Japan 2360004 0004, Japan
Citazione:
Y. Sugaya et al., "Autoradiographic studies using L-[C-14]DOPA and L-[H-3]DOPA reveal regional NA(+)-dependent uptake of the neurotransmitter candidate L-DOPA in the CNS", NEUROSCIENC, 104(1), 2001, pp. 1-14

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 localizethe uptake sites of L-DOPA in the CNS, we performed autoradiographic uptake studies using L-[C-14]DOPA and L-[H-3]DOPA in the uptake study on rat brain slice preparations, and further analyzed the properties of L-DOPA uptake. Image analysis of the L-[C-14]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. bur not dopamine (10 mM) were able to almost completely inhibit the uptake of L-[C-14]DOPA to basal levels. Microautoradiographic studies using L-[H]DOPA revealed accumulation ofdense 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, since the morphological pattern of grain accumulation was similar to that of the immunoreactivity of the glutamate aspartate transporter, a marker protein for Bergmann glial cells. In the hippocampus, the grain density significantly decreased under Nai-free conditions. In addition, grain density also decreased in the absence of Cl-. In contrast, grains in the choroid plexus and the ependymal cell layer, were not affected by the absence of Na+. These findings indicated that the uptake of L-DOPA occurs via various types of large neutral aminoacid transport mechanisms. It appears that neuronal and/or glial cells, which take up L-DOPA in a Na+-dependent manner. exist in the CNS. Our finding further supports the concept that L-DOPA itself may act as a neurotransmitter or neuromodulator. (C) 2001 IBRO. published by Elsevier Science Ltd. All rights reserved.

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Documento generato il 21/01/20 alle ore 00:50:32