title: 3-Iodothyronamine metabolism and functional effects in FRTL5 thyroid cells.
abstract: 3-Iodothyronamine (T(1)AM), produced from thyroid hormones (TH) through decarboxylation and deiodination, is a potent agonist of trace amine-associated receptor 1 (TAAR1), a G protein-coupled receptor belonging to the family of TAARs. In vivo T(1)AM induces functional effects opposite to those produced on a longer time scale by TH and might represent a novel branch of TH signaling. In this study, we investigated the action of T(1)AM on thyroid and determined its uptake and catabolism using FRTL5 cells. The expression of TAAR1 was determined by PCR and western blot in FRTL5 cells, and cAMP, iodide uptake, and glucose uptake were measured after incubation with increasing concentrations of T(1)AM for different times. T(1)AM and its catabolites thyronamine (T(0)AM), 3-iodothyroacetic acid (TA(1)), and thyroacetic acid (TA(0)) were analyzed in FRTL5 cells by HPLC coupled to tandem mass spectrometry. The product of amplification of TAAR1 gene and TAAR1 protein was demonstrated in FRTL5 cells. No persistent and dose-dependent response to T(1)AM was observed after treatment with increasing doses of this substance for different times in terms of cAMP production and iodide uptake. A slight inhibition of glucose uptake was observed in the presence of 100 μM T(1)AM after 60 and 120 min (28 and 32% respectively), but the effect disappeared after 18 h. T(1)AM was taken up by FRTL5 cells and catabolized to T(0)AM, TA(1), and TA(0) confirming the presence of deiodinase and amine oxidase activity in thyroid. In conclusion, T(1)AM determined a slight inhibition of glucose uptake in FRTL5 cells, but it was taken up and catabolized by these cells.
authors.affiliation: Dipartimento di Endocrinologia e Metabolismo, Centro Eccellenza AmbiSEN, Università di Pisa, Via Paradisa 2, 56124 Cisanello, Pisa, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Agretti
authors.forename: Giuseppina
authors.initials: G
authors.lastname: De Marco
authors.forename: Laura
authors.initials: L
authors.lastname: Russo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Saba
authors.forename: Andrea
authors.initials: A
authors.lastname: Raffaelli
authors.forename: Maja
authors.initials: M
authors.lastname: Marchini
authors.forename: Grazia
authors.initials: G
authors.lastname: Chiellini
authors.forename: Lucia
authors.initials: L
authors.lastname: Grasso
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
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
authors.forename: Massimo
authors.initials: M
authors.lastname: Tonacchera
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D002853:Chromatography, Liquid; D000242:Cyclic AMP / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D012974:Sodium Iodide / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D013961:Thyroid Gland / Q000166:cytology* / Q000378:metabolism; D013970:Thyronines / Q000378:metabolism* / Q000494:pharmacology; D013972:Thyrotropin / Q000494:pharmacology; D013974:Thyroxine / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D000095383:Trace Amine-Associated Receptors
chemical_list: D000242:Cyclic AMP; D005947:Glucose; D007453:Iodide Peroxidase; D007457:Iodine Radioisotopes; D008996:Monoamine Oxidase Inhibitors; D010293:Pargyline; D020033:Protein Isoforms; D043562:Receptors, G-Protein-Coupled; D012974:Sodium Iodide; D013970:Thyronines; D013972:Thyrotropin; D013974:Thyroxine; D000095383:Trace Amine-Associated Receptors; C487948:3-iodothyronamine; C004547:thyronamine; C507436:selenodeiodinase type 1, mouse