[Influence of NMDA receptor stimulation in brain cortex and hippocampus on NO dependent cGMP synthase. Effect of ischemia on NO related biochemical processes during recirculation].
Stimulation of NMDA receptor increases NO-dependent cGMP synthesis. A significantly higher cGMP level was observed in hippocampus (about 8-fold increase) than in cerebral cortex (2.5-fold increase), as compared to basal value. The activity of NO synthase (NOS) and the basal level of cGMP in unstimulated slices were only slightly higher in hippocampus than in the cortex. About 60% of NOS total activity was found in the brain membrane fraction. The enzyme activity was not affected by glucocorticoids, even after 20 days of hydrocortisone treatment in dose of 40 mg/kg b.w. Brain ischemia induced by ligation of the both common carotid arteries in gerbils (Meriones unquiculatus) significantly increased NOS activity as well as cGMP and putrescine concentrations but decreased mono-ADP-ribosolation of proteins. Changes of NOS activity and cGMP concentration evoked by ischemia were decreased by specific inhibitor of the neuronal form of NOS (nNOS), 7-nitrodazole and the inhibitor of guanylate cyclase, LY 83,583 administered respectively in a dose of 25 mg/kg b.w. and 6 mg/kg b.w. 5 min. before ischemia. The inhibitor of nNOS, 7NI, did not change the concentration of putrescine during ischemia and reperfusion. Our results indicated that these inhibitors could protect the brain against excessive production of nitric oxide and biochemical processes dependent on it. In this way they may offer a new strategy in the therapy of brain ischemia.
Zakładu Komórkowej Transdukeji Sygnału, Instytutu-Centrum Medycyny Doświadczalnej i Klinicznej PAN.
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Chalimoniuk
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Głód
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Strosznajder
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D006152:Cyclic GMP / Q000378:metabolism*; D005849:Gerbillinae; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D006854:Hydrocortisone / Q000627:therapeutic use; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D009569:Nitric Oxide; D016202:N-Methylaspartate; D006152:Cyclic GMP; D006854:Hydrocortisone
Wpływ stymulacji receptora NMDA w hipokampie i korze mózgu na synteze cGMP zaleznego od NO. Procesy biochemiczne tlenku azotu w okresie recyrkulacji po krótkotrwałej ischemii mózgu.