Muscimol prevents neuronal injury induced by NMDA.
The effect of muscimol on N-methyl-D-aspartate (NMDA)-induced injury of primary cultured cerebral cortical neurons was examined. NMDA induced a dose-dependent leakage of LDH activity, which was significantly inhibited by (+-)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclopentan-5,10-imine (MK-801). Muscimol significantly reduced the NMDA-induced increase of lactic dehydrogenase (LDH) leakage, and bicuculline abolished this protective effect of muscimol. Similarly, muscimol reduced the NMDA-induced increase in trypan blue staining of the cells, and bicuculline suppressed this inhibitory action of muscimol. These results suggest that GABAA-receptor stimulation exerts a protective action against the neuronal injury induced by NMDA-receptor activation.
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
S
S
Ohkuma
S H
SH
Chen
M
M
Katsura
D Z
DZ
Chen
K
K
Kuriyama
D000818:Animals; D002478:Cells, Cultured; D002493:Central Nervous System Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000517:prevention & control*; D002540:Cerebral Cortex / Q000166:cytology; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D009118:Muscimol / Q000627:therapeutic use*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D014343:Trypan Blue
D011963:Receptors, GABA-A; D009118:Muscimol; D016202:N-Methylaspartate; D007770:L-Lactate Dehydrogenase; D014343:Trypan Blue