[Effect of thrombin on survival of hippocampal neurons].
The effect of thrombin on the rat hippocampal neurons death in model of neurotoxicity induced by hemoglobin or glutamate, was studied. Thrombin (10 nM) was shown to inhibit 100-mkM glutamate--or 10-mkM hemoglobin-induced apoptosis of the rat hippocampal neurons. With the aid of PAR1 (protease-activated receptor1) agonist peptide and PAR1 antagonist, the PAR1 was found to be necessary for protective action of thrombin in hippocampal neurons in models of neurotoxicity induced by hemoglobin or glutamate. Because the prolonged elevation [Ca2+] ib neurons is a critical part of neurodestructive processes in CNS, the effect of thrombin on Ca2+-homeostatis of neurons after its injury by the inducer of neuronal apoptosis: a synthetic agonist of the NMDA receptors N-methyl-D-aspartate (NMDA), was studied. We hypothesized that thrombin via receptors PAR may prove to be neuroprotective for the hippocampus. Thrombin was shown to stimulate via PAR1 a transient increase in [Ca2+] in neurons in a concentration-dependent manner. Thrombin (1 nM) decreased the [Ca2+] signal induced by activation of the NMDA-subtype of glutamate receptors. This thrombin effect may be one of the reasons of the protective action of thrombin in hippocampal neurons.
Strukova
S M
SM
Kiseleva
E V
EV
Dugina
T N
TN
Glusa
E
E
Storozhevykh
T P
TP
Pinelis
V G
VG
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005971:Glutamates / Q000633:toxicity; D006454:Hemoglobins / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D013917:Thrombin / Q000494:pharmacology / Q000502:physiology*
D005971:Glutamates; D006454:Hemoglobins; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D013917:Thrombin; D002118:Calcium