In vivo release of dopa and dopamine from genetically engineered cells grafted to the denervated rat striatum.
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.
Horellou
P
P
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, Gif-sur-Yvette, France.
Brundin
P
P
Kalén
P
P
Mallet
J
J
Björklund
A
A
D000818:Animals; D001522:Behavior, Animal; D002396:Catechols / Q000378:metabolism; D003342:Corpus Striatum / Q000502:physiology*; D003714:Denervation; D003956:Dialysis / Q000379:methods; D004295:Dihydroxyphenylalanine / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004702:Endocrine Glands / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000637:transplantation; D005818:Genetic Engineering; D006801:Humans
D002396:Catechols; D004295:Dihydroxyphenylalanine; D004298:Dopamine