3-iodothyronamine (T1AM) is a novel relative of thyroid hormone, able to 
interact with specific G protein-coupled receptors, known as trace 
amine-associated receptors. Significant functional effects are produced by 
exogenous T1AM, including a negative inotropic and chronotropic effect in 
cardiac preparations. This work was aimed at estimating endogenous T1AM 
concentration in different tissues and determining its cardiac metabolism. A 
novel HPLC tandem mass spectrometry assay was developed, allowing detection of 
T1AM, thyronamine, 3-iodothyroacetic acid, and thyroacetic acid. T1AM was 
detected in rat serum, at the concentration of 0.3±0.03 pmol/ml, and in all 
tested organs (heart, liver, kidney, skeletal muscle, stomach, lung, and brain), 
at concentrations significantly higher than the serum concentration, ranging 
from 5.6±1.5 pmol/g in lung to 92.9±28.5 pmol/g in liver. T1AM was also 
identified for the first time in human blood. In H9c2 cardiomyocytes and 
isolated perfused rat hearts, significant Na+-dependent uptake of exogenous T1AM 
was observed, and at the steady state total cellular or tissue T1AM 
concentration exceeded extracellular concentration by more than 20-fold. In both 
preparations T1AM underwent oxidative deamination to 3-iodothyroacetic acid. 
T1AM deamination was inhibited by iproniazid but not pargyline or semicarbazide, 
suggesting the involvement of both monoamine oxidase and semicarbazide-sensitive 
amine oxidase. Thyronamine and thyroacetic acid were not detected in heart. 
Finally, evidence of T1AM production was observed in cardiomyocytes exposed to 
exogenous thyroid hormone, although the activity of this pathway was very low.