Proteinase-activated type 1 receptors are involved in the mechanism of protection of rat hippocampal neurons from glutamate toxicity.
Survival of cultured rat hippocampal neurons was estimated 4, 24, and 48 h after 15-min exposure to the toxic effect of glutamate under conditions of pre- or coincubation with 10 nM thrombin. Thrombin inhibited glutamate-induced apoptosis in neurons 24 and 48 h after treatment, but had no effect on necrosis. Selective peptide agonist of proteinase-activated type 1 receptors simulated, but receptor antagonist suppressed the neuroprotective effect of thrombin. Our results suggest that peptide antagonist of type 1 receptors play a role in the mechanisms of neuronal protection from glutamate toxicity.
Gorbacheva
L R
LR
Department of Human and Animal Physiology, Biological Faculty, M. V. Lomonosov Moscow State University.
Storozhevykh
T P
TP
Kiseleva
E V
EV
Pinelis
V G
VG
Strukova
S M
SM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology; D009474:Neurons / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044463:Receptor, PAR-1 / Q000819:agonists / Q000187:drug effects / Q000502:physiology*; D013917:Thrombin / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors
D009842:Oligopeptides; D044463:Receptor, PAR-1; C508782:mercaptopropionyl-phenylalanyl-cyclohexylalanyl-cyclohexylalanyl-arginyl-lysyl-prolyl-asparaginyl-aspartyl-lysinamide; C508781:threonyl-phenylalanyl-leucyl-leucyl-arginyl-asparagine; D018698:Glutamic Acid; D013917:Thrombin; D010975:Platelet Aggregation Inhibitors