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Lipid Peroxidation‐Induced Inhibition of γ‐Aminobutyric Acid Uptake in Rat Brain Synaptosomes: Protection by Glucocorticoids
Author(s) -
Braughler J. Mark
Publication year - 1985
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1985.tb08755.x
Subject(s) - chemistry , lipid peroxidation , xanthine oxidase , biochemistry , superoxide dismutase , aminobutyric acid , catalase , sodium , synaptosome , medicine , endocrinology , enzyme , membrane , biology , receptor , organic chemistry
Incubation of rat brain synaptosomes with xanthine and xanthine oxidase (X/XO) resulted in an inhibition of γ‐aminobutyric acid (GABA) uptake. The inhibitory effects of X/XO were temperature‐ and time‐dependent, and were characterized by an increased K m for GABA and a decresed V max . Inhibition of GABA uptake by X/XO was associated with both the formation of malonyldialdehyde (MDA) and conjugated dienes, indicating that lipid peroxidation was involved. Studies with catalase, superoxide dismutase (SOD), mannitol, and chelated iron suggested that hydroxyl radical (OH·) was probably responsible for the initiation of lipid peroxidation. Both the peroxidation of synaptosomal membranes and the inhibition of GABA uptake by X/XO were enhanced by the addition of ADP and FeCl 2 . The X/XO‐induced inhibition of GABA uptake by synaptosomes could be prevented by preincubation of synaptosomes with certain glucocorticoids prior to X/XO exposure. Methylprednisolone sodium succinate (MPSS), dexamethasone sodium phosphate (DMSP), and prednisolone sodium succinate (PSS) all prevented the inhibition of GABA uptake by X/XO. MPSS was most effective at concentrations around 100 μ M , DMSP was slightly more potent, and PSS was optimal at around 300 μ M. On the other hand, hydrocortisone sodium succinate (HCSS) was ineffective at preventing X/XO‐induced inhibition of GABA uptake at concentrations up to 3 m M. The steroids are presumed to work through a mechanism that blocked the formation of lipid peroxides, as MPSS inhibited the formation of conjugated dienes in synaptosomes exposed to X/XO at a concentration that also protected GABA uptake.