1. Rotenone enhances N-methyl-D-aspartate currents by activating a tyrosine kinase in rat dopamine neurons.
- Author
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Wu YN, Martella G, and Johnson SW
- Subjects
- Animals, Data Interpretation, Statistical, Electrophysiology, Enzyme Activation drug effects, Genistein pharmacology, Hydrogen Peroxide pharmacology, In Vitro Techniques, Male, Neurons drug effects, Oxidants pharmacology, Patch-Clamp Techniques, Rats, Rats, Sprague-Dawley, Rotenone antagonists & inhibitors, Second Messenger Systems drug effects, Second Messenger Systems physiology, Uncoupling Agents antagonists & inhibitors, Dopamine physiology, Neurons enzymology, Protein-Tyrosine Kinases metabolism, Receptors, N-Methyl-D-Aspartate agonists, Rotenone pharmacology, Uncoupling Agents pharmacology
- Abstract
Our previous work showed that the pesticide rotenone increases the amplitude of inward currents evoked by N-methyl-D-aspartate (NMDA) in substantia nigra dopamine neurons. Using patch pipettes to record whole-cell currents in rat brain slices, we report that the rotenone-induced potentiation of NMDA current is blocked by the tyrosine kinase inhibitors genistein and PP1. This action of rotenone is mimicked by H2O2, which is also blocked by genistein. Our results suggest that the rotenone-dependent increase in NMDA current is mediated by release of reactive oxygen species that activates a protein tyrosine kinase.
- Published
- 2007
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