The Cellular Mechanism of Bitter Taste Receptor Mediated Relaxation of Rat Aorta

Abstract

BackgroundBitter taste receptors, TAS2Rs, are a family of G‐protein‐coupled receptors. TAS2Rs are expressed in mucous epithelial cells of the tongue which mediate the bitter taste and can sense the potential toxins in the food. Recent studies demonstrate that these receptors are expressed in cells outside the gustatory system as well, such as several of smooth muscle tissues. The activation of TAS2Rs can increase the intracellular inositol triphosphate (IP3) thereby the activity of IP3 receptors (IP3R) on the sarcoplasmic reticulum. The Ca2+ that is released through IP3Rs, subsequently activates the large conductance Ca2+‐ and voltage‐activated K+ (BK) channels, and the activation of BK channels leads to the relaxation of smooth muscle.MethodsWe investigated the expression of TAS2Rs in rat aorta using real time qPCR, the functional effect of TAS2Rs activation on rat aortic contractility using isometric tension recordings, and the underlying cellular signaling pathways in smooth muscle cells using confocal microscopy.ResultsqPCR detected the mRNA for TAS2R107 in aorta. The TAS2R agonist, denatonium, relaxed the aorta pre‐contracted with 60 mM K+ in a concentration dependent manner with an EC50 of 215.2 μM (n=6, N=6). The addition of denatonium, as low as 10 μM, caused a transient relaxation of aorta ring pre‐contracted with L‐phynlephrine (10 μM), and the following accumulative addition of denatonium caused a concentration‐dependent further relaxation (n=6, N=6). Denatonium (500 μM) caused a transient increase of electrical field stimulation‐induced (25 Hz‐5 volts) aorta contractions followed by a complete inhibition (n=6, N=6). The confocal microscopy experiments with smooth muscle tissue suggest that the activation of TAS2Rs increased the Ca2+ transient of smooth muscle cells which may underlie the reduction of aorta contractions.ConclusionsWe conclude that the activation of TAS2Rs can reduce the tension of pre‐contracted rat aorta and the TAS2R agonists have the potential implication in the treatment of hypertension.Support or Funding InformationResearch Funding from Southwest University