Tissue distribution and cardiac metabolism of 3-iodothyronamine

Alessandro Saba, Grazia Chiellini, Sabina Frascarelli, Maja Marchini, Sandra Ghelardoni, Andrea Raffaelli, Massimo Tonacchera, Paolo Vitti, Thomas S. Scanlan, Riccardo Zucchi

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Abstract

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 T 1AM production was observed in cardiomyocytes exposed to exogenous thyroid hormone, although the activity of this pathway was very low.

Original languageEnglish (US)
Pages (from-to)5063-5073
Number of pages11
JournalEndocrinology
Volume151
Issue number10
DOIs
StatePublished - Oct 2010

ASJC Scopus subject areas

  • Endocrinology

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    Saba, A., Chiellini, G., Frascarelli, S., Marchini, M., Ghelardoni, S., Raffaelli, A., Tonacchera, M., Vitti, P., Scanlan, T. S., & Zucchi, R. (2010). Tissue distribution and cardiac metabolism of 3-iodothyronamine. Endocrinology, 151(10), 5063-5073. https://doi.org/10.1210/en.2010-0491