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Dietary trace amine‐dependent vasoconstriction in porcine coronary artery
Author(s) -
Herbert A A,
Kidd E J,
Broadley K J
Publication year - 2008
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/bjp.2008.286
Subject(s) - vasoconstriction , tyramine , chemistry , pharmacology , histamine , norepinephrine , medicine , endocrinology , receptor , vasodilation , antagonist , dopamine
Background and purpose: The dietary trace amines tyramine and β‐phenylethylamine (β‐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 β‐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. Experimental approach: The responses to p‐tyramine and β‐PEA were investigated in vitro in rings of the left anterior descending coronary arteries of pigs. Key results: p‐Tyramine induced a concentration‐dependent (0.1–3 m M ) 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. β‐PEA also produced a concentration‐dependent (0.3–10 m M ) vasoconstriction which was unaffected by endothelium removal, β‐adrenoceptor or 5‐HT receptor antagonists. A substantial, but reduced, response to β‐PEA was obtained in the presence of prazosin (α 1 ‐adrenoceptor antagonist), haloperidol (D 2 /D 3 dopamine receptor antagonist) or mepyramine (H 1 histamine receptor antagonist). The pD 2 value for β‐PEA was unaffected by any of the antagonists tested. Conclusions and implications: Vasoconstriction induced by p‐tyramine does not involve an indirect sympathomimetic effect, although vasoconstriction caused by β‐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. British Journal of Pharmacology (2008) 155 , 525–534; doi: 10.1038/bjp.2008.286 ; published online 7 July 2008