A POSSIBLE ROLE FOR TYROSINE KINASES IN THE REGULATION OF THE NEURONAL DOPAMINE TRANSPORTER IN MOUSE STRIATUM

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 inhi bitor of protein tyrosine kinases, inhibited dopamine uptake into mous e striatal homogenates with an ICH, of 18 mu M. The inhibition by geni stein 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 inhib itor. Another protein tyrosine kinase inhibitor, tyrphostin 23, also i nhibited transport but was significantly less potent than genistein. T yrphostin 25 and lavendustin A were without major effect on dopamine u ptake. In addition, the inactive structural analog of genistein, genis tin, had no significant effect on dopamine uptake. The inhibition of d opamine transport by 50 mu M genistein was accompanied by a reduction in the level of a 110-kDa band of tyrosine phosphoprotein. It is sugge sted that protein tyrosine kinases play a role in the cascade of event s which ultimately lead to regulation of neuronal dopamine transport. (C) 1997 Elsevier Science Ireland Ltd.