Rotenone enhances N-methyl-D-aspartate currents by activating a tyrosine kinase in rat dopamine neurons.
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.
Wu
Yan-Na
YN
Department of Neurology, Oregon Health and Science University, Portland, Oregon, USA.
Martella
Giuseppina
G
Johnson
Steven W
SW
D000818:Animals; D003627:Data Interpretation, Statistical; D004298:Dopamine / Q000502:physiology*; D004594:Electrophysiology; D004789:Enzyme Activation / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D016877:Oxidants / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D012402:Rotenone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D014475:Uncoupling Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D016877:Oxidants; D016194:Receptors, N-Methyl-D-Aspartate; D014475:Uncoupling Agents; D012402:Rotenone; D006861:Hydrogen Peroxide; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D004298:Dopamine