title: Tissue distribution and cardiac metabolism of 3-iodothyronamine.
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 T1AM production was observed in cardiomyocytes exposed to exogenous thyroid hormone, although the activity of this pathway was very low.
authors.affiliation: Dipartimento di Chimica e Chimica Industriale, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Saba
authors.forename: Grazia
authors.initials: G
authors.lastname: Chiellini
authors.forename: Sabina
authors.initials: S
authors.lastname: Frascarelli
authors.forename: Maja
authors.initials: M
authors.lastname: Marchini
authors.forename: Sandra
authors.initials: S
authors.lastname: Ghelardoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Raffaelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Tonacchera
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Scanlan
authors.forename: Riccardo
authors.initials: R
authors.lastname: Zucchi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000737:chemistry; D053719:Tandem Mass Spectrometry; D013970:Thyronines / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C487948:3-iodothyronamine; D013970:Thyronines