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Denatonium enhanced the tone of denuded rat aorta via bitter taste receptor and phosphodiesterase activation

Minchi Liu,Wenjun Qian,Selvaraj Subramaniyam,Shuang Liu,Wenkuan Xin

Bitter taste receptors (Tas2rs) initiate a bitter taste signaling involving the activation of taste-specific G protein gustducin and phosphodiesterases (PDEs); it leads to the decrease of cytosolic level of cyclic adenosine monophosphate (cAMP) in taste cells. Recent studies have identified the expression of Tas2rs in a variety of non-lingual tissues including vascular smooth muscle (VSM), pulmonary smooth muscle and airway smooth muscle. The current study aims to determine the expression of Tas2rs and gustducin in rat aortic smooth muscle tissue and to investigate the effect of Tas2rs agonist denatonium on the tone of isolated denuded aorta rings. Here we reported the expression of six subtypes of Tas2r mRNA and the taste receptor-associated G proteins in endothelium-denuded aorta. Immunostaining experiments showed that the protein of gustducin expressed in vascular smooth muscle cells (VSMCs). Furthermore, denatonium increased the tone of freshly isolated denuded aorta rings in a concentration-dependent manner, and the potentiation effect of denatonium was blocked by a Tas2rs antagonist adenosine 5′-monophosphate (5′-AMP), by the cAMP-hydrolyzing PDE inhibitors , and by a cAMP-synthesizing enzyme activator forskolin , respectively. The blockade of G βγ signaling did not have a negative impact on the denatonium-induced tonic contractions. These findings suggested that the functional Tas2rs and gustducin are expressed in rat aortic smooth muscle and that denatonium might increase the smooth muscle tone through a Tas2rs signaling pathway involving the activation of PDEs.