Cardiac effects of trace amines

Pharmacological characterization of trace amine-associated receptors

Sabina Frascarelli, Sandra Ghelardoni, Grazia Chiellini, Romina Vargiu, Simonetta Ronca-Testoni, Thomas (Tom) Scanlan, David Grandy, Riccardo Zucchi

Research output: Contribution to journalArticle

49 Citations (Scopus)

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, β-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, β-phenylethylamine, and tryptamine produced a dose-dependent negative inotropic effect as shown by reduced cardiac output (IC50 = 109 μM, 159 μM, and 242 μM, respectively). In the same preparation a similar effect was produced by thyronamine and 3-iodothyronamine, with IC50 = 94 μM and 27 μM, 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 [3H]-p-tyramine and [125I]-3-iodothyronamine was observed in ventricular tissue. While [3H]-p-tyramine was displaced by 3-iodothyronamine, [125I]-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 = β-phenylethylamine, while tryptamine and p-tyramine are significantly less active.

Original languageEnglish (US)
Pages (from-to)231-236
Number of pages6
JournalEuropean Journal of Pharmacology
Volume587
Issue number1-3
DOIs
StatePublished - Jun 10 2008

Fingerprint

Tyramine
Amines
Pharmacology
Octopamine
Phenethylamines
Inhibitory Concentration 50
Sympathomimetics
Biogenic Amines
Papillary Muscles
Genistein
G-Protein-Coupled Receptors
Propranolol
Cardiac Output
Protein-Tyrosine Kinases
3-iodothyronamine
Heart Rate
Hemodynamics
tryptamine
thyronamine

Keywords

  • β-Phenylethylamine
  • G-protein coupled receptor
  • Myocardial function
  • Octopamine
  • p-Tyramine
  • Signal transduction
  • Thyronamine
  • Tryptamine

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Cardiac effects of trace amines : Pharmacological characterization of trace amine-associated receptors. / Frascarelli, Sabina; Ghelardoni, Sandra; Chiellini, Grazia; Vargiu, Romina; Ronca-Testoni, Simonetta; Scanlan, Thomas (Tom); Grandy, David; Zucchi, Riccardo.

In: European Journal of Pharmacology, Vol. 587, No. 1-3, 10.06.2008, p. 231-236.

Research output: Contribution to journalArticle

Frascarelli, S, Ghelardoni, S, Chiellini, G, Vargiu, R, Ronca-Testoni, S, Scanlan, TT, Grandy, D & Zucchi, R 2008, 'Cardiac effects of trace amines: Pharmacological characterization of trace amine-associated receptors', European Journal of Pharmacology, vol. 587, no. 1-3, pp. 231-236. https://doi.org/10.1016/j.ejphar.2008.03.055
Frascarelli, Sabina ; Ghelardoni, Sandra ; Chiellini, Grazia ; Vargiu, Romina ; Ronca-Testoni, Simonetta ; Scanlan, Thomas (Tom) ; Grandy, David ; Zucchi, Riccardo. / Cardiac effects of trace amines : Pharmacological characterization of trace amine-associated receptors. In: European Journal of Pharmacology. 2008 ; Vol. 587, No. 1-3. pp. 231-236.
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