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Updated: Jul 9, 2026
07:16
Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
NO/cGMP-dependent modulation of synaptic transmission.
Robert Feil1, Thomas Kleppisch
1Interfakultäres Institut für Biochemie, Universität Tübingen, Hoppe-Seyler-Strasse, 4, 72076 München, Germany.
Handbook of Experimental Pharmacology
|December 8, 2007
Summary
Nitric oxide (NO) acts as a key messenger in the brain, influencing synaptic transmission and plasticity. This review explores NO
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Signaling
Background:
- Nitric oxide (NO) is a crucial signaling molecule in the central nervous system (CNS).
- NO mediates its effects through cyclic guanosine-3',5'-monophosphate (cGMP), impacting various cellular processes.
- cGMP signaling can be activated by NO or natriuretic peptides via guanylyl cyclases.
Purpose of the Study:
- To review the role of NO as a retrograde messenger in synaptic plasticity, particularly long-term potentiation (LTP) in the hippocampus.
- To discuss presynaptic mechanisms involving the NO/cGMP/cGKI pathway and its downstream effectors.
- To explore alternative NO/cGMP signaling pathways and their impact on synaptic activity.
Main Methods:
- Review of existing pharmacological and genetic studies.
- Analysis of literature on NO/cGMP/cGKI signaling cascades.
- Discussion of identified downstream components and alternative signaling modes.
Main Results:
- The NO/cGMP/cGKI pathway modulates transmitter release and synaptic plasticity.
- Presynaptic mechanisms involve CaMKII, VASP, RGS proteins, and alpha-synuclein.
- Alternative pathways can inhibit transmitter release and induce long-term depression (LTD).
- Emerging evidence points to cGMP signaling through CNG and HCN channels.
Conclusions:
- NO plays a significant role as a retrograde messenger in hippocampal LTP.
- Multiple downstream targets and signaling pathways contribute to NO's diverse effects on synaptic function.
- Further research is needed to fully elucidate the complex roles of NO and cGMP signaling in the CNS.
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