title: Cardiac effects of trace amines: pharmacological characterization of trace amine-associated receptors.
abstract: Trace amine-associated receptors, a novel class of G-protein coupled receptors which respond to trace amines but not to classical biogenic amines, have been found to be expressed in heart. Therefore, we investigated the cardiac effects of the trace amines p-tyramine, beta-phenylethylamine, octopamine, and tryptamine. Isolated rat hearts were perfused in the presence of trace amines, monitoring the hemodynamic variables. In addition, radioligand binding experiments with [3H]-p-tyramine and [125I]-3-iodothyronamine were performed in rat ventricular tissue. Octopamine, beta-phenylethylamine, and tryptamine produced a dose-dependent negative inotropic effect as shown by reduced cardiac output (IC(50)=109 microM, 159 microM, and 242 microM, respectively). In the same preparation a similar effect was produced by thyronamine and 3-iodothyronamine, with IC(50)=94 microM and 27 microM, respectively. The negative inotropic effect of octopamine was confirmed in a papillary muscle preparation. All trace amines except tryptamine increased the heart rate, but this action could be attributed to their sympathomimetic properties, since it was abolished by propranolol. The negative inotropic effect of trace amines was significantly increased by the tyrosine kinase inhibitor genistein. Specific and saturable binding of [(3)H]-p-tyramine and [125I]-3-iodothyronamine was observed in ventricular tissue. While [3H]-p-tyramine was displaced by 3-iodothyronamine, [(125)I]-3-iodothyronamine was not displaced by p-tyramine. In conclusion, trace amines and thyronamines are negative inotropic agents. Their effect appears to be mediated by a subtype of trace amine-associated receptor which is characterized by the rank of potency: 3-iodothyronamine > thyronamine = octopamine = beta-phenylethylamine, while tryptamine and p-tyramine are significantly less active.
authors.affiliation: Dipartimento di Scienze dell'Uomo e dell'Ambiente, University of Pisa, Pisa, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Frascarelli
authors.forename: Sandra
authors.initials: S
authors.lastname: Ghelardoni
authors.forename: Grazia
authors.initials: G
authors.lastname: Chiellini
authors.forename: Romina
authors.initials: R
authors.lastname: Vargiu
authors.forename: Simonetta
authors.initials: S
authors.lastname: Ronca-Testoni
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Scanlan
authors.forename: David K
authors.initials: DK
authors.lastname: Grandy
authors.forename: Riccardo
authors.initials: R
authors.lastname: Zucchi
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001679:Biogenic Amines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010210:Papillary Muscles / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D017982:Receptors, Biogenic Amine / Q000187:drug effects*; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism*; D013566:Sympathomimetics / Q000494:pharmacology; D013970:Thyronines / Q000494:pharmacology*; D014439:Tyramine / Q000378:metabolism; D000095383:Trace Amine-Associated Receptors
chemical_list: D000319:Adrenergic beta-Antagonists; D001679:Biogenic Amines; D011433:Propranolol; D011505:Protein-Tyrosine Kinases; D017982:Receptors, Biogenic Amine; D043562:Receptors, G-Protein-Coupled; D013566:Sympathomimetics; D013970:Thyronines; D014439:Tyramine; D000095383:Trace Amine-Associated Receptors; C487948:3-iodothyronamine; C004547:thyronamine