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Review
. 2022 Nov 16;11(22):3638.
doi: 10.3390/cells11223638.

The Complex Journey of the Calcium Regulation Downstream of TAS2R Activation

Maria Talmon  1 , Federica Pollastro  2 , Luigia Grazia Fresu  1
Affiliations
Review

The Complex Journey of the Calcium Regulation Downstream of TAS2R Activation

Maria Talmon et al. Cells. .

Abstract

Bitter taste receptors (TAS2Rs) have recently arisen as a potential drug target for asthma due to their localization in airway cells. These receptors are expressed in all cell types of the respiratory system comprising epithelial, smooth muscle and immune cells; however, the expression pattern of the subtypes is different in each cell type and, accordingly, so is their role, for example, anti-inflammatory or bronchodilator. The most challenging aspect in studying TAS2Rs has been the identification of the downstream signaling cascades. Indeed, TAS2R activation leads to canonical IP3-dependent calcium release from the ER, but, alongside, there are other mechanisms that differ according to the histological localization. In this review, we summarize the current knowledge on the cytosolic calcium modulation downstream of TAS2R activation in the epithelial, smooth muscle and immune cells of the airway system.

Keywords: bitter taste receptors; calcium signaling; epithelial lung cells; respiratory system; smooth muscle cells.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
TAS2R expression and mediated functions in human tissues: respiratory system [14,19,26,27]; gastro-intestinal tract [20,31,32]; cardiovascular system [21,22,24,33,34]; immune system [26,35,36,37,38,39]; genitourinary system [29,30,40,41,42,43,44]; skin [37,45,46]; SNC [47,48].
Figure 2
Figure 2
TAS2R signal transduction cascade in taste cells.
Figure 3
Figure 3
TAS2R expression pattern in airways cells. TAS2Rs expressed in mucociliated epithelial cells, in the solitary chemosensory cells (SCC) and smooth muscle cells are reported in the yellow, green and red boxes, respectively.
Figure 4
Figure 4
TAS2R signal transduction cascade in smooth muscle cells. 1. Cytosolic calcium increases open BKCa, leading to the outflow of K+ and, consequently, to membrane hyperpolarization. 2. TAS2R Gβγ subunit inhibits VDCC activated by a procontractile stimulus. 3. TAS2Rs promote the mitochondrial uptake of calcium released, following challenge with a procontractile stimulus.
See this image and copyright information in PMC

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