A possible role for tyrosine kinases in the regulation of the neuronal dopamine transporter in mouse striatum

J. R. Simon, D. J. Bare, B. Ghetti, J. A. Richter

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

The present investigation was undertaken to test the hypothesis that a reduction in the activity of protein tyrosine kinases would result in an alteration in dopamine transport. Genistein, a broad-spectrum inhibitor of protein tyrosine kinases, inhibited dopamine uptake into mouse striatal homogenates with an IC50 of 18 μM. The inhibition by genistein was rapid, reversible and somewhat selective, in that genistein did not inhibit the uptake of choline or GABA under similar conditions. Kinetic analyses indicated that genistein was a noncompetitive inhibitor. Another protein tyrosine kinase inhibitor, tyrphostin 23, also inhibited transport but was significantly less potent than genistein. Tyrphostin 25 and lavendustin A were without major effect on dopamine uptake. In addition, the inactive structural analog of genistein, genistin, had no significant effect on dopamine uptake. The inhibition of dopamine transport by 50 μM genistein was accompanied by a reduction in the level of a 110-kDa band of tyrosine phosphoprotein. It is suggested that protein tyrosine kinases play a role in the cascade of events which ultimately lead to regulation of neuronal dopamine transport.

Original languageEnglish (US)
Pages (from-to)201-205
Number of pages5
JournalNeuroscience Letters
Volume224
Issue number3
DOIs
StatePublished - Apr 10 1997

Keywords

  • Dopamine
  • Dopamine transporter
  • Dopamine uptake
  • Genistein
  • Tyrosine kinase

ASJC Scopus subject areas

  • Neuroscience(all)

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