Smooth muscle pharmacology

Type 2 bitter taste receptors (TAS2Rs) are a family of G-protein coupled receptors that are found on the taste buds of the tongue and palate.  As the name suggests, these receptors are normally responsible for the detection of bitter substances, and there are several thousand known natural and synthetic TAS2R agonists.  The expression of these receptors in the mouth is considered to play an important role in signalling the presence of harmful substances, thereby preventing their ingestion.  In a somewhat surprising finding, it was shown that TAS2Rs are also located on airway smooth muscle cells of the trachea and bronchioles, and that activation of these receptors leads to relaxation of the airways.  Thus, bitter taste receptor agonists are now being studied as potential novel therapies for obstructive respiratory diseases; because they are particularly efficacious airway smooth muscle relaxants and act via a different mechanism than the extensively used β-agonists.  Consistent with the studies on airway smooth muscle, there have been recent studies showing that bitter taste agonists also decrease blood pressure and relax pre-contracted vascular smooth muscle in vitro.  However, the underlying mechanisms remain unclear.  The aim of the present study is therefore to determine the mechanism underlying the relaxant effect of the bitter tastants in both airway and vascular smooth muscle.  In this regard, particular emphasis will be given to how bitter taste agonists affect Ca²⁺ signalling in smooth muscle cells as well as their ability to modulate the activity of specific ion channels.

Myography, Fluorescence microscopy, Measurement of intracellular Ca²⁺ concentration, Electrophysiology, Molecular biology, Cell culture

Lu P, Zhang CH, Lifshitz LM, ZhuGe R.  Extraoral bitter taste receptors in health and disease.  J Gen Physiol. 2017; 149(2):181-197.  doi: 10.1085/jgp.201611637.

Sai WB, Yu MF, Wei MY, Lu Z, Zheng YM, Wang YX, Qin G, Guo D, Ji G, Shen J, Liu QH.  Bitter tastants induce relaxation of rat thoracic aorta precontracted with high K⁺.  Clin Exp Pharmacol Physiol. 2014; 41(4):301-308.  doi: 10.1111/1440-1681.12217.

Deshpande DA, Robinett KS, Wang WC, Sham JS, An SS, Liggett SB.  Bronchodilator activity of bitter tastants in human tissue.  Nat Med. 2011; 17(7):776-778.  doi: 10.1038/nm0711-776b.