The serotonergic system is one of the aminergic
neurotransmitter systems participating in the maintenance of homeostasis of the organism in mammals; accordingly, it regulates the activity of various cerebral functions to organize adapted responses of the brain to environmental stimuli. The regulatory activity of the serotonergic system itself is modulated by an endogenous mechanism based on an allosteric interaction involving a newly discovered
peptide,
5-HT-moduline, and the
5-HT1B receptor which, as an
autoreceptor, controls the release of
5-HT from serotonergic neuron terminals.
5-HT-moduline specifically interacts with 5-HT1B receptors at nanomolar concentrations resulting in the desensitization of the receptor. As 5-HT1B
autoreceptors have an inhibitory effect on the release of
5-HT,
5-HT-moduline ultimately increases its release. The
peptide is characterized by several criteria which correspond to those of a
neurotransmitter, strongly suggesting that
5-HT-moduline is a novel
neuropeptide locally controlling serotonergic activity.
5-HT-moduline is released in various parts of the brain, particularly under conditions of stress; moreover, its deactivation by specific
antibodies in mice induces changes in the behavior of the animal. These results strongly suggest that the
peptide may play a role in the physiopathology of
central nervous system disorders in mammals, particularly in conditions related to stress and anxiety. Furthermore, the fact that
5-HT-moduline increases the release of
5-HT suggests that
synthetic drugs which recognize the
5-HT-moduline binding site on 5-HT1B receptors and mimic the effect of the
peptide, may have
antidepressant properties by increasing the release of
5-HT.