A Bitter Taste in Your Heart

Abstract

The human genome contains ∼29 bitter taste receptors (T2Rs), which are responsible for detecting thousands of bitter ligands, including toxic and aversive compounds. This sentinel function varies between individuals and is underpinned by naturally occurring T2R polymorphisms, which have also been associated with disease. Recent studies have reported the expression of T2Rs and their downstream signaling components within non-gustatory tissues, including the heart. Though the precise role of T2Rs in the heart remains unclear, evidence points toward a role in cardiac contractility and overall vascular tone. In this review, we summarize the extra-oral expression of T2Rs, focusing on evidence for expression in heart; we speculate on the range of potential ligands that may activate them; we define the possible signaling pathways they activate; and we argue that their discovery in heart predicts an, as yet, unappreciated cardiac physiology.

Positive selection drives the evolution of a primate bitter taste receptor gene

“…Bitter taste, one of the five basic taste qualities (umami, sweet, bitter, sour, and salty), acts as sentinels in defending animals from consuming the potentially toxic and harmful substances which often taste bitter (Chandrashekar et al., 2000; Lu et al., 2017). Bitter taste perception is mediated by the interaction between bitter tastants and bitter taste receptors which are discovered in mouth and throat, and also in extraoral positions such as brain, respiratory tract, lungs, heart, intestines, and bladder (Bloxham et al., 2020; Foster et al., 2013; Garcia‐Esparcia et al., 2013; Jeruzal‐Swiatecka et al., 2020; Shah et al., 2009).…”

Intense bitterness of molecules: Machine learning for expediting drug discovery

“…However, our results reveal that VB compounds have significantly lower QPlogHERG values than NVB compound, suggesting that VB compounds could be more cardiotoxic than NVB by blocking hERG channels, in line with previous work that found hERG channels among off-targets of bitter compounds [12] . Interestingly, T2Rs are also expressed in the heart, which raises the possibility that bitter compounds may both activate cardiac T2Rs [74] and block hERG channels [12] . In summary, our analysis shows that VB and pVB drugs tend to be less harmful as far as acute toxicity and hepatotoxicity, but have more potential to be cardiotoxic than NVB compounds.…”

Dysgeusia

“… 7 Remote taste receptors have been reported in tissues from the gastrointestinal tract, bladder, brain, respiratory tract, heart, buccal mucosa, sinuses, white blood cells, bone marrow, thyroid, keratinocytes, and testicles. 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 The functional specificity of taste cells has prompted researchers to divide them into the following 5 types: type I (glialike), type II (bitter, sweet, umami), type III (sour), type IV (pluripotent), and type V (marginal cells). 25 , 26 The older concept of “taste mapping”—representing the tongue diagrammatically and showing the relative concentrations of specific taste sensations—has been replaced largely with the newer concept that all areas of the tongue represent the different tastes almost equally ( Figure 3 ).…”

“…Through the research of the previous 2 decades, we have come to know that approximately 30 taste receptor genes code for the bitter taste. 17 , 75 Fat taste (oleogustus) is one of the newer described taste sensations and is proposed to be carried via the glossopharyngeal and chorda tympani nerves. 76 , 77 , 78 Calcium taste has been found to help modulate calcium metabolism, intake, and homeostasis in mammals and has specific receptors coded via multiple genes.…”