title: Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function.
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 microM 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, calcium-calmodulin 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 microM); 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.
authors.affiliation: Dipartimento di Scienze dell'Uomo e dell'Ambiente, University of Pisa, Pisa, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Chiellini
authors.forename: Sabina
authors.initials: S
authors.lastname: Frascarelli
authors.forename: Sandra
authors.initials: S
authors.lastname: Ghelardoni
authors.forename: Vittoria
authors.initials: V
authors.lastname: Carnicelli
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Tobias
authors.forename: Andrea
authors.initials: A
authors.lastname: DeBarber
authors.forename: Simona
authors.initials: S
authors.lastname: Brogioni
authors.forename: Simonetta
authors.initials: S
authors.lastname: Ronca-Testoni
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cerbai
authors.forename: David K
authors.initials: DK
authors.lastname: Grandy
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Scanlan
authors.forename: Riccardo
authors.initials: R
authors.lastname: Zucchi
mesh_terms: D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry; D013970:Thyronines / Q000494:pharmacology*
chemical_list: C487948:3-iodothyronamine; D017931:DNA Primers; D013970:Thyronines