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

• Published in: British journal of pharmacology Vol. 165; no. 7; pp. 2191 - 2202
• Main Authors: Anwar, MA, Ford, WR, Broadley, KJ, Herbert, AA
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2012; Nature Publishing Group
• Subjects: 5‐HT receptors; Animals; Biological and medical sciences; In Vitro Techniques; Male; Medical sciences; Mesenteric Arteries - drug effects; Mesenteric Arteries - physiology; mesenteric vasculature; NG-Nitroarginine Methyl Ester - pharmacology; Perfusion; Pharmacology. Drug treatments; Phenethylamines - pharmacology; Phenylephrine - pharmacology; rat; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A - drug effects; Receptor, Serotonin, 5-HT2A - physiology; Receptors, Serotonin - drug effects; Receptors, Serotonin - physiology; Research Papers; Ritanserin - pharmacology; Serotonin - pharmacology; trace amines; trace amine‐associated receptors; tryptamine; Tryptamines - pharmacology; tyramine; Tyramine - pharmacology; Vasoconstriction - drug effects; Vasodilation - drug effects; β‐phenylethylamine; Tyramine; Tryptamine; Vasodilator agent; mesenteric vasculature; Rat; Rodentia; Vasoconstriction; Mesentery; Sympathomimetic; Serotonine receptor; trace amines; 5-HT receptors; Vascularization; trace amine-associated receptors; Vasomotricity; Vertebrata; Mammalia; Amine; β-phenylethylamine; Animal; Vasoconstrictor agent; Comparative study; Biological receptor
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.2011.01706.x

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.