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Nitric oxide: an endogenous anticonvulsant substance
A Buisson1, N Lakhmeche, C Verrecchia
1Laboratoire de Pharmacologie, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, Paris, France.
Abstract:
In the present study, we examine the involvement of the L-arginine-nitric oxide pathway in seizure activity termination. Convulsions were induced reproducibly by intracerebroventricular administration of N-methyl-D-aspartate to conscious mice. The duration of the seizure activity was increased by inhibition of the NO-pathway or by intracerebroventricular injection of methylene blue, an inhibitor of guanylate cyclase activity. This increased duration in seizure activity was reversed by co-administration of L-arginine or by intracerebroventricular injection of guanosine 3':5' cyclic monophosphate (cGMP). These results suggest that nitric oxide produced in response to NMDA receptor activation leads to an increase in cGMP which induces the seizure activity termination.
Insights
The L-arginine-nitric oxide (NO) pathway terminates seizure activity. Inhibiting this pathway prolonged seizures, but L-arginine or cGMP administration reversed the effect, suggesting NO/cGMP
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Seizure activity involves complex neurological pathways.
- The L-arginine-nitric oxide (NO) pathway plays a role in various physiological processes.
- Understanding mechanisms of seizure termination is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the role of the L-arginine-nitric oxide pathway in terminating seizure activity.
- To elucidate the signaling cascade involving NO and cyclic guanosine monophosphate (cGMP) in seizure cessation.
Main Methods:
- Seizures were induced in conscious mice via intracerebroventricular administration of N-methyl-D-aspartate (NMDA).
- The NO-pathway was inhibited, and guanylate cyclase activity was blocked using methylene blue.
- Effects on seizure duration were assessed, and interventions with L-arginine and cGMP were evaluated.
Main Results:
- Inhibition of the NO-pathway significantly increased seizure duration.
- Administration of methylene blue also prolonged seizure activity.
- Co-administration of L-arginine or direct injection of cGMP reversed the prolonged seizure duration.
Conclusions:
- The L-arginine-nitric oxide pathway is critically involved in the termination of seizure activity.
- NMDA receptor activation leads to nitric oxide production, increasing cGMP levels.
- Elevated cGMP levels appear to induce the cessation of seizures, highlighting a potential therapeutic target.