Is there a role for biogenic amine receptors in mediating trace
amine-induced vascular contraction?
Abstract
Background and Purposes: Substantial evidence indicates trace amines can
induce vasoconstriction independently of noradrenaline release. However,
the mechanism underlying noradrenaline-independent vasoconstrictor
responses to trace amines has not yet been established. This study
evaluates the role of trace amine-associated receptor 1 (TAAR1) and
other biogenic amine receptors in mediating trace amine-induced
vasoconstriction. Experimental Approach: Vasoconstrictor responses to
β-PEA and the TAAR1-selective agonist, RO5256390 were assessed in vitro
in endothelium-denuded aortic rings and third-order mesenteric arteries
of male Sprague Dawley rats. Key Results: β-PEA and RO5256390 induced
concentration-dependent vasoconstriction of aortic rings but not
third-order mesenteric arteries. Vasoconstrictor responses in aortic
rings were insensitive to antagonists of 5-HT and dopamine. The
murine-selective TAAR1 antagonist, EPPTB, had no effect on either β-PEA
or RO5256390-induced vasoconstriction. The α1-adrenoceptor antagonist,
prazosin, and the α2-adrenoceptor antagonist, yohimbine, induced a small
but significant shift of the β-PEA concentration response curve that
could not be ascribed to blockade of α1- or α2-adrenoceptors. Conclusion
and Implications: Vasoconstrictor responses to trace amines are not
mediated by classical biogenic amine neurotransmitter receptors.
Although β-PEA vasoconstrictor responses were insensitive to ETTP, it
has low affinity for rat TAAR1. Therefore, we propose that TAAR1 remains
the most likely candidate receptor mediating vasoconstrictor responses
to trace amines and that prazosin and yohimbine have some affinity for
TAAR1.