Neuromodulators and transmitters in respiratory control

The respiratory control system is influenced by classical neurotransmitters and by neuromodulators. The neuromodulators are neuroactive substances that can be secreted at a distance from their receptors and must diffuse to their site of action. Their function can be nonsynaptic and long lasting, and their effect can be direct or indirect via other neuroactive substances. In the central nervous system, a variable degree of mismatch exists between sites of neuromodulator secretion and reception. The assignment of a natural role for a neuromodulator in respiratory control is strengthened by evidence from a variety of experimental approaches, including localization of receptor sites in respiratory-related areas and evidence for natural binding of neuromodulators to these receptors, neurophysiological and respiratory responses to the neuromodulators and their antagonists, and, finally, modulation of specific respiratory responses by neuromodulator antagonists to document the role of the endogenous modulator in eliciting the original response. Neuromodulators that are considered seriously as natural participants in respiratory control include dopamine in peripheral chemoreception and adenosine, endorphins (including enkephalins), serotonin, and substance P in central respiratory regulation.