Abstract
3-Iodothyronamine (T1AM) is the last iodinated thyronamine generated from thyroid hormone alternative metabolism found circulating in rodents and in humans. So far, the physiopathological meaning of T1AM tissue levels is unknown. Much is instead known on T1AM pharmacological effects in rodents. Such evidence indicates that T1AM acutely modifies, with high potency and effectiveness, rodents’ metabolism and behavior, often showing inverted U-shaped dose–response curves. Although several possible targets for T1AM were identified, the mechanism underlying T1AM behavioral effects remains still elusive. T1AM pharmacokinetic features clearly indicate the central nervous system is not a preferential site for T1AM distribution but it is a site where T1AM levels are critically regulated, as it occurs for neuromodulators or neurotransmitters. We here summarize and discuss evidence supporting the hypothesis that central effects of T1AM derive from activation of intracellular and possibly extracellular pathways. In this respect, consisting evidence indicates the intracellular pathway is mediated by the product of T1AM phase-I non-microsomal oxidation, the 3-iodothryoacetic acid, while other data indicate a role for the trace amine-associated receptor, isoform 1, as membrane target of T1AM (extracellular pathway). Overall, these evidence might sustain the non-linear dose–effect curves typically observed when increasing T1AM doses are administered and reveal an interesting and yet unexplored link between thyroid, monoamine oxidases activity and histamine.
Highlights
3-Iodothyronamine (T1AM) is the last iodinated thyronamine produced by thyroid hormone (TH) metabolism and supposed to mediate TH non-genomic effects
From its identification in rodent tissues [1], T1AM was included within the family of the trace amines (TAs) and identified as an endogenous ligand for trace amine-associated receptors (TAARs), a family of constitutively active G protein-coupled receptors with species and tissue-specific expression cross-talking with the dopaminergic and the serotoninergic transmission [2, 3]
We here summarize and discuss evidence indicating that beha vioral effects of T1AM deserve to receive the attention of the investigators since, in the central nervous system, the pharma cokinetic features of this amine include a novel role for mito chondrial monoamine oxidases (MAO)
Summary
3-Iodothyronamine (T1AM) is the last iodinated thyronamine produced by thyroid hormone (TH) metabolism and supposed to mediate TH non-genomic effects. From its identification in rodent tissues [1], T1AM was included within the family of the trace amines (TAs) and identified as an endogenous ligand for trace amine-associated receptors (TAARs), a family of constitutively active G protein-coupled receptors with species and tissue-specific expression cross-talking with the dopaminergic and the serotoninergic transmission [2, 3]. This latter feature raised the interest around TAAR agonists, and on T1AM, as potential treatments for controlling craving, pain, and neuropsychiatric illnesses. We here summarize and discuss evidence indicating that beha vioral effects of T1AM deserve to receive the attention of the investigators since, in the central nervous system, the pharma cokinetic features of this amine include a novel role for mito chondrial monoamine oxidases (MAO)
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