In vivo release of dopa and dopamine from genetically engineered cells grafted to the denervated rat striatum.

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.

journal_name

Neuron

journal_title

Neuron

authors

Horellou P,Brundin P,Kalén P,Mallet J,Björklund A

doi

10.1016/0896-6273(90)90078-t

subject

Has Abstract

pub_date

1990-10-01 00:00:00

pages

393-402

issue

4

eissn

0896-6273

issn

1097-4199

pii

0896-6273(90)90078-T

journal_volume

5

pub_type

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