Searching for mechanisms of N-methyl-D-aspartate-induced glutathione efflux in organotypic hippocampal cultures.
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.
Wallin
Camilla
C
Department of Medical Biophysics, University of Göteborg, Medicinaregatan 11, S-405 30 Göteborg, Sweden.
Abbas
Abdul-Karim
AK
Tranberg
Mattias
M
Weber
Stephen G
SG
Wigström
Holger
H
Sandberg
Mats
M
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
D010714:Phosphatidylethanolamines; D013449:Sulfonamides; D013654:Taurine; D016202:N-Methylaspartate; C017967:W 7; D005978:Glutathione; D011796:Quinacrine; D011112:Polymyxin B