Signal transduction and modulating pathways in tryptamine-evoked vasopressor responses of the rat isolated perfused mesenteric bed

Anwar, Mohammad Akhtar, Ford, William Richard ORCID: https://orcid.org/0000-0002-8792-6169, Herbert, Amy Angharad and Broadley, Kenneth John ORCID: https://orcid.org/0000-0002-3339-2050 2013. Signal transduction and modulating pathways in tryptamine-evoked vasopressor responses of the rat isolated perfused mesenteric bed. Vascular Pharmacology 58 (1-2) , pp. 140-149. 10.1016/j.vph.2012.10.007

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Abstract

Tryptamine is an endogenous and dietary indoleamine-based trace amine implicated in cardiovascular pathologies, including hypertension, migraine and myocardial infarction. This study aimed at identifying the signalling pathways for the vasoconstrictor response to tryptamine in rat isolated perfused mesenteric arterial beds and co-released vasodilator modulators of tryptamine-mediated vasoconstriction. Tryptamine caused concentration-dependent vasoconstriction of the mesenteric bed, measured as increases in perfusion pressure. These were inhibited by the 5-HT2A receptor antagonist, ritanserin, indicating mediation via 5-HT2A receptors. The response was inhibited by the phospholipase C (PLC) and phospholipase A2 (iPLA2) inhibitors, U-73122 and PACOCF3, suggesting involvement of phospholipase pathways. Activation of these pathways by tryptamine releases cyclooxygenase (COX) products since indomethacin (non-selective inhibitor of COX-1/2) and nimesulide (selective COX-2 inhibitor) reduced the vasoconstriction. The most likely COX vasoconstrictor product was prostaglandin PGE2 since the responses to tryptamine were reduced by AH-6809, a non-selective EP1 receptor antagonist. Involvement of the Rho-kinase pathway in the tryptamine-evoked vasoconstriction was also indicated by its reduction by the Rho-kinase inhibitors, Y-27,632 and fasudil. The tryptamine vasoconstriction is modulated by the co-released endothelial vasodilator, nitric oxide. Thus, circulating tryptamine can regulate mesenteric blood flow through a cascade of signalling pathways secondary to stimulation of 5-HT2A receptors.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	Tryptamine; Rat mesenteric artery; Vasoconstriction; 5-HT2A receptors; Nitric oxide
Publisher:	Elsevier
ISSN:	1537-1891
Funders:	Wellcome Trust, British Heart Foundation
Date of First Compliant Deposit:	30 March 2016
Last Modified:	13 May 2023 00:30
URI:	https://orca.cardiff.ac.uk/id/eprint/52470

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