Nitric Oxide as a Neuronal Messenger

Abstract

Nitric oxide is a novel chemical agent that is used by neurons and glia in the nervous system to communicate with one another. It is used to convey and modulate information, and thereby shape behaviour.

Keywords: neurotransmitter; neuromodulator; nitric oxide; guanylyl cyclase; nitric oxide synthase; cyclic GMP

Figure 1.

Diverse nitric oxide (NO) synaptic signalling pathways from an NO source neuron to target neurons. The source neuron may contain nitric oxide synthase (NOS) as well as a conventional neurotransmitter stored in vesicles. NOS binds to calmodulin (CAM) in the presence of calcium (Ca2+), which enters the cell through an ion channel (open red bars) and converts arginine (ARG) to citrulline (CIT) and NO. NO diffuses widely over many possible pathways shown by the arrows. NO may inhibit NOS by negative feedback, activate guanylyl cyclase (GC), react with membrane or synaptic vesicle protein thiol groups (RS), or metal‐containing molecules (M) such as haemoglobin, affect ion channels and postsynaptic G protein‐coupled receptors. Ion channels may be either activated or inactivated by cyclic guanosine monophosphate (cGMP) or protein kinase G (PKG). GTP, guanosine triphosphate.

Figure 2.

Comparison of the homologous regions of Drosophila nitric oxide synthase (DNOS) and rat neuronal NOS (NNOS). Similar cofactor binding sites are found for calmodulin (CAM), flavin mononucleotide (FMN), flavin–adenine dinucleotide (FAD) and reduced nicotinamide–adenine dinucleotide phosphate (NADPH). Each contains a haem binding site (H), a phosphorylation site (P) and putative membrane binding motifs near the N‐terminus. In DNOS, it consists of repeated glutamine residues (Q), and in NNOS the N‐terminus residues form a PDZ motif.

Figure 3.

Diverse functional pathways of nitric oxide (NO) action. (a) NO acting as an orthograde neurotransmitter. Ca2+ influx through an ion channel activates nitric oxide synthase (NOS) and the NO stimulates guanylyl cyclase (GC) in the postsynaptic neuron. (b) NO serving as an orthograde cotransmitter with a conventional neurotransmitter stored in vesicles. (c) NO acting as a retrograde neurotransmitter, which is released from the postsynaptic neuron and modulates subsequent conventional neurotransmitter release from the presynaptic neuron. NOS is activated by calcium influx into the postsynaptic neuron during activation of the conventional transmitter receptor (red triangles). (d) NO acting in a paracrine fashion as it travels some distance from its source to affect neighbouring neurons. It is shown affecting ion channels (open blue bars), transmitter release and neuron receptors within a brain compartment containing several nerve terminals. NO may also act in an autocrine way by feedback action on the ion channels of the source neuron.

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Further Reading

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Jacklet, Jon W(Sep 2005) Nitric Oxide as a Neuronal Messenger. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0004093]