Cardiac effects of 3-iodothyronamine: A new aminergic system modulating cardiac function

Grazia Chiellini, Sabina Frascarelli, Sandra Ghelardoni, Vittoria Carnicelli, Sandra C. Tobias, Andrea DeBarber, Simona Brogioni, Simonetta Ronca-Testoni, Elisabetta Cerbai, David K. Grandy, Thomas S. Scanlan, Riccardo Zucchi

Research output: Contribution to journalArticle

98 Scopus citations

Abstract

3-iodothyronamine T1AM is a novel endogenous thyroid hormone derivative that activates the G protein-coupled receptor known as trace anime-associated receptor 1 (TAAR1). In the isolated working rat heart and in rat cardiomyocytes, T1AM produced a reversible, dose-dependent negative inotropic effect (e.g., 27±5, 51±3, and 65±2% decrease in cardiac output at 19, 25, and 38 μM concentration, respectively). An independent negative chronotropic effect was also observed. The hemodynamic effects of T1AM were remarkably increased in the presence of the tyrosine kinase inhibitor genistein, whereas they were attenuated in the presence of the tyrosine phosphatase inhibitor vanadate. No effect was produced by inhibitors of protein kinase A, protein kinase C, calciumcalmodulin kinase II, phosphatidylinositol-3-kinase, or MAP kinases. Tissue cAMP levels were unchanged. In rat ventricular tissue, Western blot experiments with antiphosphotyrosine antibodies showed reduced phosphorylation of microsomal and cytosolic proteins after perfusion with synthetic T1AM; reverse transcriptase-polymerase chain reaction experiments revealed the presence of transcripts for at least 5 TAAR subtypes; specific and saturable binding of [125I]T1AM was observed, with a dissociation constant in the low micromolar range (5 μM); and endogenous T1AM was detectable by tandem mass spectrometry. In conclusion, our findings provide evidence for the existence of a novel aminergic system modulating cardiac function.

Original languageEnglish (US)
Pages (from-to)1597-1608
Number of pages12
JournalFASEB Journal
Volume21
Issue number7
DOIs
StatePublished - May 2007

Keywords

  • G protein-coupled receptors
  • Myocardial function
  • Signal transduction
  • Thyronamines

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Chiellini, G., Frascarelli, S., Ghelardoni, S., Carnicelli, V., Tobias, S. C., DeBarber, A., Brogioni, S., Ronca-Testoni, S., Cerbai, E., Grandy, D. K., Scanlan, T. S., & Zucchi, R. (2007). Cardiac effects of 3-iodothyronamine: A new aminergic system modulating cardiac function. FASEB Journal, 21(7), 1597-1608. https://doi.org/10.1096/fj.06-7474com