Abstract

Introduction: 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. Methods: Kidneys were isolated and perfused with Krebs’ solution, gassed with 95% oxygen and 5% carbon dioxide, through the renal artery. Results: In preparations pre-constricted with methoxamine (5 × 10<sup>−6</sup><sc>m</sc>), T1AM (10<sup>−10</sup> – 10<sup>−6</sup> mol), RO5263397 (10<sup>−10</sup> – 10<sup>−6</sup> mol), and tryptamine (10<sup>−10</sup> – 10<sup>−6</sup> mol) produced dose-dependent vasodilator responses. EPPTB (1 × 10<sup>−6</sup><sc>m</sc>), a selective TAAR1 antagonist, had no effect on vasodilator responses induced by these agonists. A higher concentration of EPPTB (3 × 10<sup>−5</sup><sc>m</sc>) 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<sup>−4</sup><sc>m</sc>), an inhibitor of nitric oxide synthesis. The vasodilator responses were significantly reduced by inhibiting calcium-activated (tetraethylammonium, 1 × 10<sup>−3</sup><sc>m</sc>) and voltage-activated (4-AP, 1 × 10<sup>−3</sup><sc>m</sc>) potassium channels. Tryptamine-, T1AM-, and RO5263397-induced vasodilator responses were significantly reduced by BMY7378, a 5-HT<sub>1A</sub> receptor antagonist. Conclusion: 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-HT<sub>1A</sub> receptors.

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