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.