NO/cGMP-dependent modulation of synaptic transmission.
Nitric oxide (NO) is a multifunctional messenger in the CNS that can signal both in antero- and retrograde directions across synapses. Many effects of NO are mediated through its canonical receptor, the soluble guanylyl cyclase, and the second messenger cyclic guanosine-3',5'-monophosphate (cGMP). An increase of cGMP can also arise independently of NO via activation of membrane-bound particulate guanylyl cyclases by natriuretic peptides. The classical targets of cGMP are cGMP-dependent protein kinases (cGKs), cyclic nucleotide hydrolysing phosphodiesterases, and cyclic nucleotide-gated (CNG) cation channels. The NO/cGMP/cGK signalling cascade has been linked to the modulation of transmitter release and synaptic plasticity by numerous pharmacological and genetic studies. This review focuses on the role of NO as a retrograde messenger in long-term potentiation of transmitter release in the hippocampus. Presynaptic mechanisms of NO/cGMP/cGK signalling will be discussed with recently identified potential downstream components such as CaMKII, the vasodilator-stimulated phosphoprotein, and regulators of G protein signalling. NO has further been suggested to increase transmitter release through presynaptic clustering of a-synuclein. Alternative modes of NO/cGMP signalling resulting in inhibition of transmitter release and long-term depression of synaptic activity will also be addressed, as well as anterograde NO signalling in the cerebellum. Finally, emerging evidence for cGMP signalling through CNG channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels will be discussed.
Interfakultäres Institut für Biochemie, Universität Tübingen, Hoppe-Seyler-Strasse, 4, 72076 München, Germany.
Robert
R
Feil
Thomas
T
Kleppisch
D000818:Animals; D006152:Cyclic GMP / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D009569:Nitric Oxide; D006152:Cyclic GMP