Abstract
Trace amines such as p-tyramine, p-octopamine and p-synephrine are found in low concentrations in animals and plants. Consumption of pre-workout supplements containing these plant-derived amines has been associated with cardiovascular side effects. The aim of this study was to determine the mechanisms of action of these trace amines on porcine isolated coronary and mesenteric arteries. Noradrenaline caused contraction of mesenteric arteries and relaxation of coronary arteries. In both tissues, all three trace amines induced contractions with similar potencies and responses were unaffected by the β-adrenoceptor antagonist propranolol (1 µM), the nitric oxide synthase inhibitor L-NNA (100 µM), or the TAAR-1 antagonist, EPPTB (100 nM). However, the contractile responses of mesenteric arteries, but not coronary arteries, were significantly reduced by depletion of endogenous noradrenaline. Mesenteric responses to all three amines were abolished in the presence of prazosin (1 µM) whereas residual contractile responses remained in the coronary artery which were inhibited by a high concentration (100 µM) of EPPTB. The results suggest complex responses of the coronary artery to the trace amines, with activity at α1-adrenoceptors and potentially TAARs other than TAAR-1. In contrast the actions of the amines on the mesenteric artery appeared to involve indirect sympathomimetic actions and direct actions on α1-adrenoceptors.
Highlights
Noradrenaline caused contraction of mesenteric arteries and relaxation of coronary arteries
(1 μM) whereas residual contractile responses remained in the coronary artery which were inhibited by a high concentration (100 μM) of EPPTB
The results suggest complex responses of the coronary artery to the trace amines, with activity at α1-adrenoceptors and potentially trace amine-associated receptors (TAARs) other than Trace amine-associated receptor 1 (TAAR-1)
Summary
Noradrenaline caused contraction of mesenteric arteries and relaxation of coronary arteries In both tissues, all three trace amines induced contractions with similar potencies and responses were unaffected by the β-adrenoceptor antagonist propranolol (1 μM), the nitric oxide synthase inhibitor L-NNA (100 μM), or the TAAR-1 antagonist, EPPTB (100 nM). P-Tyramine (tyramine), p-octopamine (octopamine) and p-synephrine (synephrine) are substituted phenethylamines with a phenolic hydroxyl group in the para-position (Fig. 1) They are found in nanomolar concentrations in the mammalian nervous system and have been described as “trace amines”[1]. Octopamine and synephrine have been shown to exert weak direct β1-adrenoceptor agonist effects on isolated cardiac tissues and to activate cloned β2-adrenoceptors[10,11]. There is some indirect evidence to suggest that tyramine and synephrine may induce some vascular responses via specific receptors
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