3-Iodothyronamine

3-Iodothyronamine (T1AM) is an <a href="/facts/Endogenous/DFkSLkRI">endogenous</a> <a href="/facts/Thyronamine/WdsK1Tux">thyronamine</a>. It is a high-<a href="/facts/Affinity_(pharmacology)/44QLL4eU">affinity</a> <a href="/facts/Ligand_(biochemistry)/44QLL4eU">ligand</a> of the <a href="/facts/Trace_amine-associated_receptor_1/Xf3Qpjtw">trace amine-associated receptor 1</a> (TAAR1). T1AM is the most <a href="/facts/Potency_(pharmacology)/D38FDyPh">potent</a> <a href="/facts/Endogenous/DFkSLkRI">endogenous</a> TAAR1 <a href="/facts/Agonist/nz8U5NNp">agonist</a> yet discovered. It is also an <a href="/facts/Agonist/nz8U5NNp">agonist</a> of the <a href="/facts/TAAR2/FIkm6Qnh">TAAR2</a> and <a href="/facts/TAAR5/rG4czXCA">TAAR5</a> with similar <a href="/facts/Potency_(pharmacology)/D38FDyPh">potency</a> as for the TAAR1 (all in the case of the human proteins). T1AM is not a ligand of the <a href="/facts/Thyroid_hormone_receptor/7fBRzmmo">thyroid hormone receptors</a>. However, it is additionally a ligand of various <a href="/facts/Monoamine_receptor/7GKo3Fvn">monoamine</a> and other <a href="/facts/Receptor_(biochemistry)/tjTAC76a">receptors</a>. For instance, it is a <a href="/facts/Muscarinic_acetylcholine_receptor/caIdoqrW">muscarinic acetylcholine receptor</a> <a href="/facts/Antimuscarinic/802fuzgC">antagonist</a>.
Activation of TAAR1 by T1AM results in the production of large amounts of <a href="/facts/Cyclic_adenosine_monophosphate/flK2vwUe">cyclic adenosine monophosphate</a> (cAMP). This effect is coupled with decreased <a href="/facts/Thermoregulation/V692hIjw">body temperature</a> and <a href="/facts/Cardiac_output/7JCDn6Ht">cardiac output</a>. Wu et al. have pointed out that this relationship is not typical of the <a href="/facts/Endocrine_system/PDvN5cpj">endocrine system</a>, indicating that TAAR1 activity may not be coupled to <a href="/facts/G_protein/HKkcfgGP">G proteins</a> in some <a href="/facts/Tissue_(biology)/H7CpML7A">tissues</a>, or that T1AM may interact with other receptor subtypes. T1AM may be part of a <a href="/facts/Signaling_pathway/6oYAVP9I">signaling pathway</a> to modulate <a href="/facts/Cardiac/fF4KSGdk">cardiac</a> function, as the compound can induce negative <a href="/facts/Inotropic/A58XE1pa">inotropic</a> effects and decrease <a href="/facts/Cardiac_output/7JCDn6Ht">cardiac output</a>.
T1AM has been found to produce TAAR1-dependent <a href="/facts/Tyrosine_hydroxylase/n3YFThJ5">tyrosine hydroxylase</a> (TH) <a href="/facts/Phosphorylation/LXUEEeIL">phosphorylation</a> in mouse <a href="/facts/Dorsal_striatum/MjNnTjSd">dorsal striatum</a> <a href="/facts/Brain_slice/GGyICUqC">slices</a>. This phosphorylation would be expected to promote the <a href="/facts/Functional_activity/nz8U5NNp">functional activity</a> of TH. Accordingly, higher rates of <a href="/facts/Levodopa/4R7qahlh">L-DOPA</a> accumulation were observed after administration of T1AM in mice treated with a <a href="/facts/DOPA_decarboxylase_inhibitor/mLdpwIc3">DOPA decarboxylase inhibitor</a>. The preceding effects were absent with TAAR1 <a href="/facts/Knockout_mice/Aw50cobf">knockout mice</a> or with the TAAR1 <a href="/facts/Receptor_antagonist/PuXHVNdV">antagonist</a> <a href="/facts/EPPTB/XE2kPAA1">EPPTB</a>. In addition, T1AM-mediated TH phosphorylation appeared to be mediated by <a href="/facts/CaMKII/hklT8LuH">CaMKII</a> and <a href="/facts/Protein_kinase_A/kaKoYfbp">protein kinase A</a> (PKA) signaling. T1AM was also found to increase electrically evoked <a href="/facts/Dopamine/5gNy8Xkd">dopamine</a> release in striatal slices, which was blunted in TAAR1 knockout mice and in mice treated with EPPTB, indicating partial mediation by the TAAR1. In contrast to T1AM, the <a href="/facts/Trace_amine/WXRDyUMH">trace amines</a> <a href="/facts/%25CE%2592-phenethylamine/XyjysSul">β-phenethylamine</a> and <a href="/facts/Tyramine/4qCvDzcl">tyramine</a> reduced TH phosphorylation, which was independent of the TAAR1, and hence do not appear to augment TH functional activity.
T1AM had no effect on <a href="/facts/Locomotor_activity/trhhYTVR">locomotor activity</a> in rodents at low doses but produced <a href="/facts/Hypolocomotion/HPekWj74">hypolocomotion</a> at high doses.

3-Iodothyronamine open-in-new

3-Iodothyronamine