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The nitric oxide-cyclic GMP pathway plays an essential role in both promoting cell survival of cerebellar granule cells in culture and protecting the cells against ethanol neurotoxicity.
- Source :
-
Journal of neurochemistry [J Neurochem] 1998 May; Vol. 70 (5), pp. 1826-38. - Publication Year :
- 1998
-
Abstract
- NMDA has two beneficial effects on primary neuronal cultures of cerebellar granule cells (CGCs) established from 10-day-old rat pups. First, NMDA is neurotrophic and will enhance survival of CGCs in culture in the absence of ethanol. Second, ethanol exposure will induce cell death in CGC cultures, and NMDA can lessen this ethanol-induced cell loss, i.e., NMDA is neuroprotective. Because NMDA can stimulate production of nitric oxide (NO), which can in turn enhance synthesis of cyclic GMP, this study tested the hypothesis that the NO-cyclic GMP pathway is essential for NMDA-mediated neurotrophism and neuroprotection. Inhibiting the synthesis of NO with N(G)-nitro-L-arginine methyl ester eliminated both the NMDA-mediated neurotrophic and neuroprotective effects. Similarly, inhibiting production of cyclic GMP with the agent LY83583 also abolished these effects. The NO generator 2,2'-(hydroxynitrosohydrazono) bisethanamine produced neurotrophic and neuroprotective effects that were similar to those induced by NMDA. Also, 8-bromo-cyclic GMP produced neurotrophic and neuroprotective effects that were quite similar to the effects produced by NMDA. In conclusion, NMDA enhances survival of cerebellar granule cells and protects the cells against ethanol-induced cell death by a mechanism(s) that involves the NO-cyclic GMP pathway.
- Subjects :
- Aminoquinolines pharmacology
Animals
Cell Survival drug effects
Cell Survival physiology
Cells, Cultured
Cerebellum cytology
Cerebellum drug effects
Cyclic GMP antagonists & inhibitors
Dose-Response Relationship, Drug
Enzyme Inhibitors
N-Methylaspartate pharmacology
NG-Nitroarginine Methyl Ester pharmacology
Neuroprotective Agents pharmacology
Nitroso Compounds pharmacology
Rats
Rats, Sprague-Dawley
Cerebellum physiology
Cyclic GMP metabolism
Ethanol poisoning
Neurons drug effects
Neurons physiology
Nitric Oxide metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3042
- Volume :
- 70
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 9572266
- Full Text :
- https://doi.org/10.1046/j.1471-4159.1998.70051826.x