Title

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

Document Type

Article

Peer Reviewed

1

Publication Date

5-1-1998

NLM Title Abbreviation

J Neurochem

Journal/Book/Conference Title

Journal of neurochemistry

PubMed ID

9572266

Start Page

1826

End Page

1838

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.

Keywords

Aminoquinolines/pharmacology, Animals, Cell Survival/drug effects/physiology, Cells, Cultured, Cerebellum/cytology/drug effects/physiology, Cyclic GMP/antagonists & inhibitors/metabolism, Dose-Response Relationship, Drug, Enzyme Inhibitors, Ethanol/poisoning, N-Methylaspartate/pharmacology, NG-Nitroarginine Methyl Ester/pharmacology, Neurons/drug effects/physiology, Neuroprotective Agents/pharmacology, Nitric Oxide/metabolism, Nitroso Compounds/pharmacology, Rats, Rats, Sprague-Dawley

Published Article/Book Citation

Journal of neurochemistry, 70:5 (1998) pp.1826-1838.

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URL

https://ir.uiowa.edu/obgyn_pubs/232