Constrictor and dilator responses to tryptamine in the isolated perfused mesenteric arterial circulation of the rat

Mohammad Anwar, William Ford, Kenneth Broadley. Cardiff University, Cardiff, United Kingdom.

Background: Tryptamine (TTA) interacts with serotonin (5-HT; Bradley et al 1985) and trace amine-associated receptors (TAARs; Lindemann et al 2005), and is vasoactive. Rat tissues express 15 TAARs (Grandy 2007), and a similar number of 5-HT receptors (Alexander et al 2008). However, there is a paucity of data on TTA-associated effects in resistance-size arteries, particularly the mesentery. Based on these assertions, we hypothesise that the rat mesentery will display a duality in arterial responses to TTA, both constrictor and dilator. The aims of this investigation were to demonstrate the vascular reactivity to TTA in the rat mesentery and to identify the receptor(s) involved.

Methods: Male Sprague-Dawley rats were stunned and killed by cervical dislocation. The superior mesenteric artery was cannulated, and the mesenteric arterial bed excised and placed in a perfusion chamber. The bed was perfused at constant flow rate (4 mL min-1) with warmed 37°C and gassed (95% O2, 5% CO2) Krebs’ bicarbonate solution (pH 7.4). Changes in perfusion pressure were measured with a pressure transducer (Elcomatic EM 750) connected to a computer data acquisition system (AD Instruments Powerlab Chart 5). Dose-response curves (DRCs) for TTA by bolus injection (100μL volume) were constructed in the absence and repeated in the presence of prazosin (α 1- adrenoceptor inhibitor, 10 nM), phentolamine (α 1- and 2–adrenoceptor blocker, 1μM) and ritanserin (5-HT2A receptor antagonist, 100pM). In addition, responses to TTA were determined in pre-constricted (10μM phenylephrine) vascular beds in the presence of ritanserin (100pM) alone and with SB269970 (5-HT7 receptor antagonist, 10nM). Each inhibitor was infused from 20 min before the second DRC. Geometric mean ED50 with 95% confidence limits and mean Emax (± SEM) values were computed.

Results: Tryptamine caused dose-related vasoconstriction ED50, which was unaffected by prazosin (n = 4), but attenuated by phentolamine ED50. Ritanserin abolished the TTA vasoconstrictions. In phenylephrine pre-constricted mesentery with continuous perfusion of ritanserin or ritanserin and SB269970, TTA evoked vasodilatation of arteries with maxima of 64±6% and 63±1%, respectively.

Conclusion: Tryptamine induces vasoconstriction via 5-HT2A receptors, which when blocked revealed vasodilator responses in pre-constricted vessels. These were not therefore due to 5-HT7 or 5-HT2A receptors as they were not blocked by SB269970 or ritanserin. TAARs may participate in this vasodilatation and the vasoconstriction, since it was partially blocked by phentolamine which binds to TAARs (Grandy 2007).

Alexander SP et al (2008) Br J Pharmacol 153 (Suppl 2): S1-S209.
Bradley PB et al (1985) Br J Pharmacol 84: 919-925.
Grandy DK (2007) Pharmacol Ther 116: 355-390.
Lindemann L et al (2005) Genomics 85: 372-385.

MAA was funded by a Wellcome Trust Research Fellowship.