Is there a role for biogenic amine receptors in mediating β-phenylethylamine and RO5256390-induced vascular contraction?

Voisey, Alexander C. ORCID: https://orcid.org/0000-0001-6906-9397, Broadley, Harrison D., Broadley, Kenneth J. ORCID: https://orcid.org/0000-0002-3339-2050 and Ford, William R. ORCID: https://orcid.org/0000-0002-8792-6169 2024. Is there a role for biogenic amine receptors in mediating β-phenylethylamine and RO5256390-induced vascular contraction? European Journal of Pharmacology 981 , 176895. 10.1016/j.ejphar.2024.176895

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Abstract

Background: 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 β-phenylethylamine and the TAAR-1 selective agonist RO5256390-induced vasoconstriction. Methods: 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. 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 shift of the β-PEA concentration response curve too small to be ascribed to antagonism of α1- or α2-adrenoceptors, respectively. The α2-adrenoceptor antagonist atipamezole had no effect on β-PEA or RO5256390-induced vasoconstriction. Conclusion: Vasoconstrictor responses to trace amines are not mediated by classical biogenic amine neurotransmitter receptors. Insensitivity of β-PEA vasoconstrictor responses to EPPTB, may be explained by its low affinity for rat rather than murine TAAR1. Therefore, TAAR1 remains the most likely candidate receptor mediating vasoconstrictor responses to trace amines and that prazosin and yohimbine have low affinity for TAAR1.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Pharmacy
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Start Date: 2024-08-15
Publisher:	Elsevier
ISSN:	0014-2999
Date of First Compliant Deposit:	19 August 2024
Date of Acceptance:	12 August 2024
Last Modified:	21 Aug 2024 09:20
URI:	https://orca.cardiff.ac.uk/id/eprint/171472

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