Trace Amines and Trace Amine-Associated Receptors: A New Frontier in Cell Signaling

Trace amines, including β-phenylethylamine, p-octopamine, p-tyramine, and tryptamine, are produced in high levels in invertebrates where they play major roles in homeostasis regulation in a manner similar to that of adrenergic systems in mammals (Rutigliano et al. in Front Pharmacol 8:987, 2017; Gainetdinov et al. in Pharmacol Rev 70(3):549-620, 2018; Nagaya et al. in Neurosci Lett 329(3):324-328, 2002). In mammals, however, their levels are very low, initially prompting these molecules to be termed "trace" or "minor" amines in mammals with only a secondary role in the regulation of more abundant biogenic amines including catecholamines and serotonin (Gainetdinov et al. in Pharmacol Rev 70(3):549-620, 2018). The more recent discovery of trace amine-associated receptors (TAARs) revealed major, previously unsuspected roles of the trace amines and has led to increasing interest within the scientific community. For example, TAARs have been proposed to modulate signaling through dopamine (Schwartz et al. in Expert Opin Ther Targets 22(6):513-526, 2018). Furthermore, these receptors are implicated in both numerous physiological functions including regulation of sleep, olfaction, metabolism, and immunity as well in disease (e.g., substance abuse, neuropsychiatric disorders) (Gainetdinov et al. in Pharmacol Rev 70(3):549-620, 2018; Rutigliano et al. in Front Pharmacol 8:987, 2017). Consequently, trace amine and TAAR research is rapidly growing and is of great translational relevance. In this Special Issue, leaders in trace amine and TAAR research offer both reviews and original research papers that cover a wide range of topics from involvement of TAAR signaling in metabolic regulation and neurophysiology to implications of this signaling in neuropsychiatric diseases including substance abuse and schizophrenia. While a diverse range of topics is covered by these works, the common theme running through all of them is the increasing awareness that trace amine and TAAR signaling represent novel signaling mechanisms in the brain and periphery. These topics are both highly timely and of considerable importance not only for those working in the field but also for the neuroscience community at large.