Evidence that acidosis alters the high-affinity dopamine uptake in rat striatal slices and synaptosomes by different mechanisms partially related to oxidative damage.
Several experimental studies have shown that acidosis impairs neurotransmitter uptake processes. The purpose of this study was to determine the mechanism underlying acidosis-induced alterations of the high-affinity dopamine (DA) uptake in rat striatal synaptosomes and slices. Acidosis (pH 5.5) performed either by lactic acid or phosphoric acid induced a decrease in the high-affinity DA uptake in the two striatal models, slices being lesser affected than synaptosomes. Addition of the acid prior to uptake measurement led to a strong reduction of the DA uptake velocity. This early inhibitory effect was completely reversed when acid was removed from the medium by washings. Conversely, when slices and synaptosomes were pre-incubated for different times with each acid, DA uptake remained inhibited in spite of washings. This later inhibition was accompanied by the production of thiobarbituric acid reactive substances, a marker of lipid peroxidation, and was partially prevented by the antioxidant Trolox. Taken together, these results suggest that acidosis, in a degree encountered during ischemia, alters the high-affinity DA uptake by at least two ways: an early and direct effect of H(+) ions on the DA transporters, and subsequently an inhibition partially mediated by free radical damage.
Barrier
Laurence
L
Groupe d'Etudes des Mécanismes Cellulaires de l'Ischémie (GEMCI), UPRES EA 1223, Faculté de Médecine et de Pharmacie, 34 Rue du Jardin des Plantes, BP 199, 86005 Poitiers Cedex, France. lbarrier@univ-poitiers.fr
Barc
Stéphanie
S
Fauconneau
Bernard
B
Pontcharraud
Raymond
R
Kelani
Adidjath
A
Bestel
Emilie
E
Page
Guylène
G
D000138:Acidosis / Q000378:metabolism*; D000140:Acidosis, Lactic / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D003470:Culture Media; D004298:Dopamine / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D019344:Lactic Acid / Q000494:pharmacology / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress; D010756:Phosphoric Acids / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D000975:Antioxidants; D002839:Chromans; D003470:Culture Media; D010756:Phosphoric Acids; D017392:Thiobarbituric Acid Reactive Substances; D019344:Lactic Acid; C030242:phosphoric acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D004298:Dopamine