Oxygen radicals differentially affect Na+/Cl(-)-dependent transporters.
Incubation with the oxygen radical-generating enzyme, xanthine oxidase, dramatically reduced striatal dopamine transporter activity, but was unexpectedly without effect on rat hippocampal norepinephrine uptake. To determine whether environmental differences between the striatum and hippocampus contributed to this lack of oxidative effect on norepinephrine transporters, synaptosomal gamma-aminobutyric acid (GABA) uptake was assessed in both regions. Xanthine oxidase similarly decreased [3H]GABA uptake in both the striatum and hippocampus, supporting the conclusion that environmental differences did not account for the lack of effect on norepinephrine transport. These data suggest that norepinephrine transporters are less vulnerable than other Na+/Cl(-)-dependent transporters to oxidative inactivation.
Haughey
H M
HM
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112, USA.
Brown
J M
JM
Fleckenstein
A E
AE
Hanson
G R
GR
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002713:Chlorine / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000502:physiology*; D012964:Sodium / Q000502:physiology; D013566:Sympathomimetics / Q000378:metabolism; D014793:Visual Cortex / Q000187:drug effects / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D017382:Reactive Oxygen Species; D013566:Sympathomimetics; D002713:Chlorine; D005680:gamma-Aminobutyric Acid; D012964:Sodium; D014969:Xanthine Oxidase; D004298:Dopamine; D009638:Norepinephrine