Dietary trace amine-dependent vasoconstriction in porcine coronary artery.
OBJECTIVE
The dietary trace amines tyramine and beta-phenylethylamine (beta-PEA) can increase blood pressure. However, the mechanisms involved in the vascular effect of trace amines have not been fully established. The purpose of this study was to evaluate whether trace amine-dependent vasoconstriction was brought about by tyramine and beta-PEA acting as indirect sympathomimetic agents, as previously assumed, or whether trace amine-dependent vasoconstriction could be mediated by recently discovered trace amine-associated (TAA) receptors.


METHODS
The responses to p-tyramine and beta-PEA were investigated in vitro in rings of the left anterior descending coronary arteries of pigs.


RESULTS
p-Tyramine induced a concentration-dependent (0.1-3 mM) vasoconstriction. The maximum response and pD(2) value for p-tyramine was unaffected by endothelium removal or pre-treatment with antagonists for adrenoceptors, histamine, dopamine or 5-HT receptors. beta-PEA also produced a concentration-dependent (0.3-10 mM) vasoconstriction which was unaffected by endothelium removal, beta-adrenoceptor or 5-HT receptor antagonists. A substantial, but reduced, response to beta-PEA was obtained in the presence of prazosin (alpha(1)-adrenoceptor antagonist), haloperidol (D(2)/D(3) dopamine receptor antagonist) or mepyramine (H(1) histamine receptor antagonist). The pD(2) value for beta-PEA was unaffected by any of the antagonists tested.


CONCLUSIONS
Vasoconstriction induced by p-tyramine does not involve an indirect sympathomimetic effect, although vasoconstriction caused by beta-PEA may occur, in part, by this mechanism. We therefore propose that trace amine-dependent vasoconstriction is mediated by phenylethylamine-specific receptors, which are closely related to or identical to TAA receptors. These receptors could provide a target for new antihypertensive therapies.
Herbert
A A
AA
Division of Pharmacology, Welsh School of Pharmacy, Cardiff University, Cardiff, South Wales, UK.
Kidd
E J
EJ
Broadley
K J
KJ
D000818:Animals; D001679:Biogenic Amines / Q000008:administration & dosage / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D010627:Phenethylamines / Q000008:administration & dosage / Q000494:pharmacology*; D017982:Receptors, Biogenic Amine / Q000187:drug effects / Q000378:metabolism; D013552:Swine; D013566:Sympathomimetics / Q000008:administration & dosage / Q000494:pharmacology*; D014439:Tyramine / Q000008:administration & dosage / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D001679:Biogenic Amines; D010627:Phenethylamines; D017982:Receptors, Biogenic Amine; D013566:Sympathomimetics; C029261:phenethylamine; D014439:Tyramine