title: Evidence that acidosis alters the high-affinity dopamine uptake in rat striatal slices and synaptosomes by different mechanisms partially related to oxidative damage.
abstract: 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.
authors.affiliation: 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
authors.forename: Laurence
authors.initials: L
authors.lastname: Barrier
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Barc
authors.forename: Bernard
authors.initials: B
authors.lastname: Fauconneau
authors.forename: Raymond
authors.initials: R
authors.lastname: Pontcharraud
authors.forename: Adidjath
authors.initials: A
authors.lastname: Kelani
authors.forename: Emilie
authors.initials: E
authors.lastname: Bestel
authors.forename: Guylène
authors.initials: G
authors.lastname: Page
mesh_terms: 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
chemical_list: 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