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

Neuron. 1990 Oct;5(4):393-402. doi: 10.1016/0896-6273(90)90078-t.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal
  • Catechols / metabolism
  • Corpus Striatum / physiology*
  • Denervation
  • Dialysis / methods
  • Dihydroxyphenylalanine / metabolism*
  • Dopamine / metabolism*
  • Endocrine Glands / cytology
  • Endocrine Glands / metabolism*
  • Fibroblasts / metabolism*
  • Fibroblasts / transplantation
  • Genetic Engineering*
  • Humans


  • Catechols
  • Dihydroxyphenylalanine
  • Dopamine