In vivo release of dopa and dopamine from genetically engineered cells grafted to the denervated rat striatum.
Neuron
; 5(4): 393-402, 1990 Oct.
Article
em En
| MEDLINE
| ID: mdl-2119630
ABSTRACT
Fibroblastic 3T3 and endocrine RIN cells were genetically modified by infection with a recombinant retrovirus encoding the form I of human tyrosine hydroxylase (TH) and selection in tyrosine-free medium. These cells were grafted to rats unilaterally lesioned with 6-hydroxy-dopamine. Both cell types survived implantation into the striatum, expressed TH immunoreactivity, and as assessed by microdialysis 8-9 days after implantation, secreted high amounts of DOPA and/or dopamine into the surrounding host striatum. The modified 3T3 cells secreted large amounts of DOPA that was efficiently decarboxylated to dopamine by the host striatal tissue; the newly synthesized dopamine was stored only to a limited extent in the denervated striatum. The modified RIN cells synthesized dopamine that was stored intracellularly and released in a regulated fashion. The grafted DOPA-secreting cells produced 4-5 times higher extracellular dopamine levels than the dopamine-secreting cells, and they were more efficient in reducing apomorphine-induced rotation. No effect was observed with either cell type on amphetamine-induced turning behavior.
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Base de dados:
MEDLINE
Assunto principal:
Di-Hidroxifenilalanina
/
Dopamina
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Engenharia Genética
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Corpo Estriado
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Glândulas Endócrinas
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Fibroblastos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
1990
Tipo de documento:
Article