Modification of Dopamine Transporter Function: Effect of Reactive Oxygen Species and Dopamine
Article first published online: 23 NOV 2002
Journal of Neurochemistry
Volume 67, Issue 2, pages 593–600, August 1996
How to Cite
Berman, S. B., Zigmond, M. J. and Hastings, T. G. (1996), Modification of Dopamine Transporter Function: Effect of Reactive Oxygen Species and Dopamine. Journal of Neurochemistry, 67: 593–600. doi: 10.1046/j.1471-4159.1996.67020593.x
- Issue published online: 23 NOV 2002
- Article first published online: 23 NOV 2002
- Received December 6, 1995; revised manuscript received March 4, 1996; accepted March 15, 1996.
- Free radicals;
- Dopamine uptake;
- Parkinson's disease;
Abstract: Dopamine can oxidize to form reactive oxygen species and quinones, and we have previously shown that dopamine quinones bind covalently to cysteinyl residues on striatal proteins. The dopamine transporter is one of the proteins at risk for this modification, because it has a high affinity for dopamine and contains several cysteinyl residues. Therefore, we tested whether dopamine transport in rat striatal synaptosomes could be affected by generators of reactive oxygen species, including dopamine. Uptake of [3H]dopamine (250 nM) was inhibited by ascorbate (0.85 mM; −44%), and this inhibition was prevented by the iron chelator diethylenetriaminepentaacetic acid (1 mM), suggesting that ascorbate was acting as a prooxidant in the presence of iron. Preincubation with xanthine (500 µM) and xanthine oxidase (50 mU/ml) also reduced [3H]dopamine uptake (−76%). Preincubation with dopamine (100 µM) caused a 60% inhibition of subsequent [3H]dopamine uptake. This dopamine-induced inhibition was attenuated by diethylenetriaminepentaacetic acid (1 mM), which can prevent iron-catalyzed oxidation of dopamine during the preincubation, but was unaffected by the monoamine oxidase inhibitor pargyline (10 µM). None of these incubations caused a loss of membrane integrity as indicated by lactate dehydrogenase release. These findings suggest that reactive oxygen species and possibly dopamine quinones can modify dopamine transport function.