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Vasoconstrictor and vasodilator responses to tryptamine of rat-isolated perfused mesentery: comparison with tyramine and β-phenylethylamine

Anwar, Mohammad Akhtar, Ford, William Richard, Broadley, Kenneth John and Herbert, Amy Angharad 2012. Vasoconstrictor and vasodilator responses to tryptamine of rat-isolated perfused mesentery: comparison with tyramine and β-phenylethylamine. British Journal of Pharmacology 165 (7) , pp. 2191-2202. 10.1111/j.1476-5381.2011.01706.x

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Abstract

BACKGROUND AND PURPOSE Tryptamine increases blood pressure by vasoconstriction, but little is known about its actions on the mesentery, in particular the resistance arteries. Tryptamine interacts with trace amine-associated receptors (TAARs) and because of its structural similarity to 5-HT, it may also interact with 5-HT receptors. Our hypothesis is therefore that the rat mesenteric arterial bed will exhibit vasopressor and vasodepressor responses to tryptamine via both 5-HT and TAARs. EXPERIMENTAL APPROACH Tryptamine-evoked responses were assayed from pressure changes of the rat-isolated mesenteric vasculature perfused at constant flow rate in the absence and presence of adrenoceptor and 5-HT receptor antagonists. KEY RESULTS Tryptamine caused dose-dependent vasoconstriction of the mesenteric arterial bed as increases in perfusion pressure. These were unaffected by the α1-adrenoceptor antagonist, prazosin, but were attenuated by the non-selective α-adrenoceptor antagonist, phentolamine. The 5-HT2A receptor antagonists, ketanserin and ritanserin, abolished the tryptamine-induced pressure increases to reveal vasodilator responses in mesenteric beds preconstricted with phenylephrine. These tryptamine-induced vasodilator responses were unaffected by the 5-HT7 receptor antagonist, SB269970, but were eliminated by the NOS inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME). Tyramine and β-phenylethylamine also caused vasodilatation in pre-constricted vasculature, which was also abolished by L-NAME. CONCLUSIONS AND IMPLICATIONS Tryptamine causes vasoconstriction of the mesenteric vasculature via 5-HT2A receptors, which when inhibited exposed vasorelaxant effects in pre-constricted tissues. The vasodilatation was independent of 5-HT2A and 5-HT7 receptors but like that for tyramine and β-phenylethylamine was due to NO release. Potency orders suggest TAAR involvement in the vasodilatation by these trace amines.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: mesenteric vasculature; rat; trace amines; trace amine-associated receptors; 5-HT receptors; tryptamine; tyramine; β-phenylethylamine
Publisher: Wiley-Blackwell
ISSN: 0007-1188
Last Modified: 04 Jun 2017 04:32
URI: http://orca.cf.ac.uk/id/eprint/40657

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