Vasodilator Effect of Trace Amines, 3-Iodothyronamine, and RO5263397 in the Rat Perfused Kidney: Comparison with Tryptamine

Trace amine-associated receptors (TAARs) are a family of G protein-coupled receptors and are widely distributed in the body. Activation of TAAR1 by specific agonists can produce a variety of physiological effects centrally and peripherally. The objective of this study was to investigate the vasodilator effect of two selective TAAR1 agonists 3-iodothyronamine (T1AM) and RO5263397 in the isolated perfused rat kidney preparation.Kidneys were isolated and perfused with Krebs' solution, gassed with 95% oxygen and 5% carbon dioxide, through the renal artery.In preparations pre-constricted with methoxamine (5 × 10-6m), T1AM (10-10 - 10-6 mol), RO5263397 (10-10 - 10-6 mol), and tryptamine (10-10 - 10-6 mol) produced dose-dependent vasodilator responses. EPPTB (1 × 10-6m), a selective TAAR1 antagonist, had no effect on vasodilator responses induced by these agonists. A higher concentration of EPPTB (3 × 10-5m) produced a sustained increase in perfusion pressure but did not affect vasodilator responses to tryptamine, T1AM, and RO5263397. Agonist-induced vasodilator responses were slightly reduced by the removal of the endothelium but were not affected by L-NAME (1 × 10-4m), an inhibitor of nitric oxide synthesis. The vasodilator responses were significantly reduced by inhibiting calcium-activated (tetraethylammonium, 1 × 10-3m) and voltage-activated (4-AP, 1 × 10-3m) potassium channels. Tryptamine-, T1AM-, and RO5263397-induced vasodilator responses were significantly reduced by BMY7378, a 5-HT1A receptor antagonist.It was concluded that vasodilator responses produced by the TAAR1 agonists, T1AM, RO5263397, and tryptamine, were not mediated via TAAR1 but were probably via activation of 5-HT1A receptors.