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Nitric oxide transforms serotonin into an inactive form and this affects neuromodulation
P Fossier1, B Blanchard, C Ducrocq
1Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS, Gif sur Yvette, France.
Neuroscience
|August 28, 1999
Summary
Nitric oxide (NO) modifies serotonin, reducing its ability to regulate synaptic transmission. This interaction, involving NO-derived chemicals, impacts neurological functions and highlights free radical roles in the nervous system.
Area of Science:
- Neuroscience
- Biochemistry
- Molecular Biology
Background:
- Nitric oxide (NO) is a ubiquitous signaling molecule in the central nervous system.
- NO and its derivatives can interact with neuromodulators, potentially altering synaptic transmission.
- Serotonin is a key neuromodulator involved in regulating mood and sleep-wake cycles.
Purpose of the Study:
- To investigate the modulatory effect of serotonin on acetylcholine release in Aplysia.
- To determine if nitric oxide influences serotonin's modulatory action.
- To elucidate the chemical mechanisms underlying the interaction between nitric oxide and serotonin.
Main Methods:
- Utilized an identified cholinergic synapse in the Aplysia buccal ganglion.
- Applied serotonin and measured evoked acetylcholine release.
- Investigated the effects of a nitric oxide donor (3-morpholinosydnonimine) and nitric oxide synthase activation on serotonin's action.
- Analyzed serotonin chemical derivatives using analytical techniques.
Main Results:
- Extracellularly applied serotonin decreased evoked acetylcholine release.
- The modulatory effect of serotonin was significantly reduced in the presence of nitric oxide (NO donor or endogenous NO).
- Chemical modifications of serotonin, including dimerization and nitrosation/nitration, were observed.
- These serotonin derivatives (e.g., 4-nitroso-serotonin, 4-nitro-serotonin) did not replicate serotonin's modulatory effect.
Conclusions:
- Nitric oxide chemically modifies serotonin, forming derivatives that are ineffective in modulating synaptic transmission.
- These findings reveal a novel interaction between free radicals and neuromediators with implications for nervous system function.
- The chemical alteration of serotonin by NO may have consequences in both physiological and pathological conditions affecting mood and other central functions.
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