Abstract

Trace amines are endogenous compounds, found in the nervous system of all species, and consist of 2-phenylethylamine, p-tyramine, p-octopamine, and tryptamine. In vertebrates synthesis occurs by the enzymatic decarboxylation of l-amino acids via aromatic l-amino acid decarboxylase, with p-octopamine formed from p-tyramine by dopamine-β-hydroxylase. Trace amine synthesis by decarboxylation is reciprocally regulated by the pervading monoaminergic tone. Once synthesized, trace amines are neither stored in synaptic vesicles, released in an activity-dependent manner, nor released via exocytosis, with effects mediated by a family of trace amine-associated receptors (TAARs). In contrast, in invertebrates trace amines act as traditional neurotransmitters, released in an activity-dependent manner, with effects mediated by dedicated tyramine and octopamine receptors evolutionarily distinct from TAAR. Thus the ability to synthesize and use trace amines in neuronal signaling appears to have arisen at least twice during evolution.

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