title: Searching for mechanisms of N-methyl-D-aspartate-induced glutathione efflux in organotypic hippocampal cultures.
abstract: N-Methyl-D-aspartate (NMDA)-receptor stimulation evoked a selective and partly delayed elevated efflux of glutathione, phosphoethanolamine, and taurine from organotypic rat hippocampus slice cultures. The protein kinase inhibitors H9 and staurosporine had no effect on the efflux. The phospholipase A2 inhibitors quinacrine and 4-bromophenacyl bromide, as well as arachidonic acid, a product of phospholipase A2 activity, did not affect the stimulated efflux. Polymyxin B, an antimicrobal agent that inhibits protein kinase C, and quinacrine in high concentration (500 microM), blocked efflux completely. The stimulated efflux after but not during NMDA incubation was attenuated by a calmodulin antagonist (W7) and an anion transport inhibitor (DNDS). Omission of calcium increased the spontaneous efflux with no or small additional effects by NMDA. In conclusion, NMDA receptor stimulation cause an increased selective efflux of glutathione, phosphoethanolamine and taurine in organotypic cultures of rat hippocampus. The efflux may partly be regulated by calmodulin and DNDS sensitive channels.
authors.affiliation: Department of Medical Biophysics, University of Göteborg, Medicinaregatan 11, S-405 30 Göteborg, Sweden.
authors.forename: Camilla
authors.initials: C
authors.lastname: Wallin
authors.forename: Abdul-Karim
authors.initials: AK
authors.lastname: Abbas
authors.forename: Mattias
authors.initials: M
authors.lastname: Tranberg
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Weber
authors.forename: Holger
authors.initials: H
authors.lastname: Wigström
authors.forename: Mats
authors.initials: M
authors.lastname: Sandberg
mesh_terms: D000818:Animals; D001692:Biological Transport; D005978:Glutathione / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D016202:N-Methylaspartate / Q000494:pharmacology*; D010714:Phosphatidylethanolamines / Q000378:metabolism; D011112:Polymyxin B / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D013654:Taurine / Q000378:metabolism
chemical_list: D010714:Phosphatidylethanolamines; D013449:Sulfonamides; D013654:Taurine; D016202:N-Methylaspartate; C017967:W 7; D005978:Glutathione; D011796:Quinacrine; D011112:Polymyxin B