Novel neural modulators

Annu Rev Neurosci. 2003;26:105-31. doi: 10.1146/annurev.neuro.26.041002.131047.


The discovery that nitric oxide (NO) is produced by neurons and regulates synaptic activity has challenged the definition of a neurotransmitter. NO is not stored in synaptic vesicles and does not act at conventional receptors on the surface of adjacent neurons. The toxic gases carbon monoxide (CO) and hydrogen sulfide (H2S) are also produced by neurons and modulate synaptic activity. D-serine synthesis and release by astrocytes as an endogenous ligand for the "glycine" site of N-methyl D-aspartate (NMDA) receptors defy the concept that a neurotransmitter must be synthesized by neurons. We review the properties of these "atypical" neural modulators.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acids / metabolism*
  • Animals
  • Carbon Monoxide / metabolism*
  • Guanylate Cyclase
  • Humans
  • Hydrogen Sulfide / metabolism
  • Muscle, Smooth / physiology
  • Neurons / metabolism*
  • Neurotransmitter Agents / classification
  • Neurotransmitter Agents / metabolism*
  • Nitric Oxide / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Soluble Guanylyl Cyclase
  • Synapses / metabolism*
  • Synaptic Transmission


  • Amino Acids
  • Neurotransmitter Agents
  • Receptors, Cytoplasmic and Nuclear
  • Nitric Oxide
  • Carbon Monoxide
  • Guanylate Cyclase
  • Soluble Guanylyl Cyclase
  • Hydrogen Sulfide