title: Vasoconstrictor and vasodilator responses to tryptamine of rat-isolated perfused mesentery: comparison with tyramine and β-phenylethylamine.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: Division of Pharmacology, Welsh School of Pharmacy, Cardiff University, Cardiff, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Anwar
authors.forename: W R
authors.initials: WR
authors.lastname: Ford
authors.forename: K J
authors.initials: KJ
authors.lastname: Broadley
authors.forename: A A
authors.initials: AA
authors.lastname: Herbert
mesh_terms: D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010477:Perfusion; D010627:Phenethylamines / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology*; D014439:Tyramine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D010627:Phenethylamines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D014363:Tryptamines; C104425:serotonin 7 receptor; D016713:Ritanserin; D010656:Phenylephrine; C029261:phenethylamine; D012701:Serotonin; C030820:tryptamine; D019331:NG-Nitroarginine Methyl Ester; D014439:Tyramine