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Vasoconstrictor and vasodilator responses to tryptamine of rat‐isolated perfused mesentery: comparison with tyramine and β‐phenylethylamine
Author(s) -
Anwar MA,
Ford WR,
Broadley KJ,
Herbert AA
Publication year - 2012
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 - 10.1111/j.1476-5381.2011.01706.x
Subject(s) - phentolamine , vasoconstriction , vasodilation , prazosin , tryptamine , endocrinology , chemistry , mesenteric arteries , medicine , tyramine , pharmacology , phenylephrine , serotonin , receptor , antagonist , biology , biochemistry , artery , blood pressure
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 α 1 ‐adrenoceptor antagonist, prazosin, but were attenuated by the non‐selective α‐adrenoceptor antagonist, phentolamine. The 5‐HT 2A 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‐HT 7 receptor antagonist, SB269970, but were eliminated by the NOS inhibitor, N ω ‐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‐HT 2A receptors, which when inhibited exposed vasorelaxant effects in pre‐constricted tissues. The vasodilatation was independent of 5‐HT 2A and 5‐HT 7 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.