Investigation of Trace Amines Associated Receptors in Rat Aorta

Abstract

Trace amines (TAs) including β‐phenylethylamine (β‐PEA) and tyramine are usually regarded as indirectly acting sympathomimetic amines (ISAs) exerting vasoconstriction via α1‐adrenoceptors (α1‐AR). However, they can additionally stimulate trace amine‐associated receptors (TAARs). Human and rat TAAR1 and human TAAR4 are mainly activated by β‐PEA and tyramine and rat TAAR4 by β‐PEA and tryptamine. We aimed to examine vasoconstriction by TAs and to identify the TAAR1 in rat aorta by molecular biology. By using a rabbit anti‐human anti‐rat polyclonal TAAR 1 antibody we identified the TAAR1 (40kDa) in rat aorta by Western Blotting. Further, we identified the sequence of TAAR1 by PCR using rat cDNA from aortic tissue. β‐PEA, octopamine and D‐amphetamine contracted the rat aorta but tyramine was a weak partial agonist. Therefore, tyramine was examined as a potential antagonist of the other TAs. We found a significant inhibition (P<0.05) by tyramine (1mM) of the contractile responses to single doses (100μM) of β‐PEA (n=5), octopamine (n=5) and D‐amphetamine (n=3) to 41.5±15.5%, 15.1±5.1% and 4.4±13.1%, respectively of the pre‐tyramine values in the presence prazosin (1μM), cocaine (10μM), ICI‐118,551 (1μM) and pargyline (10μM). The weak contractile activity of tyramine in the rat aorta and antagonism of the other TAs suggests that tyramine is a weak partial agonist/antagonist of TAARs in this tissue. Funding: Cardiff University