Evidence that acidosis alters the high-affinity dopamine uptake in rat striatal slices and synaptosomes by different mechanisms partially related to oxidative damage |
| |
Authors: | Barrier Laurence Barc Stéphanie Fauconneau Bernard Pontcharraud Raymond Kelani Adidjath Bestel Emilie Page Guylène |
| |
Institution: | 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 |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|