scholarly journals Bitter Taste Receptors as Regulators of Abdominal Muscles Contraction

2019 ◽  
pp. 991-995
Author(s):  
P. Zagorchev ◽  
G.V. Petkov ◽  
H.S. Gagov

Bitter taste receptors (TAS2R) are expressed in many non-sensor tissues including skeletal muscles but their function remains unexplored. The aim of this study is to investigate the role of TAS2R in rat abdominal skeletal muscles contractions using denatonium, a TAS2R agonist. Low concentration of denatonium (0.01 mmol/l) caused a significant decrease of amplitudes of the electrical field stimulation (EFS)-induced contractions in abdominal skeletal muscles preparations in vitro. This inhibitory effect was significantly reduced when the preparations were pre-incubated with gentamicin (0.02 mmol/l) used as a non-specific inhibitor of IP3 formation or with BaCl(2) (0.03 mmol/l) applied to block the inward-rectifier potassium current. All experiments were performed in the presence of pipecuronium in order to block the nerve stimulation of the contractions. The data obtained suggest that denatonium decreases the force of rat abdominal muscles contractions mainly via activation of TAS2R, phosphatidylinositol 4,5-biphosphate and its downstream signal metabolites.

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5891
Author(s):  
Sofie Zehentner ◽  
Agnes T. Reiner ◽  
Christoph Grimm ◽  
Veronika Somoza

Background: Since it is known that bitter taste receptors (TAS2Rs) are expressed and functionally active in various extra-oral cells, their genetic variability and functional response initiated by their activation have become of broader interest, including in the context of cancer. Methods: A systematic research was performed in PubMed and Google Scholar to identify relevant publications concerning the role of TAS2Rs in cancer. Results: While the findings on variations of TAS2R genotypes and phenotypes and their association to the risk of developing cancer are still inconclusive, gene expression analyses revealed that TAS2Rs are expressed and some of them are predominately downregulated in cancerous compared to non-cancerous cell lines and tissue samples. Additionally, receptor-specific, agonist-mediated activation induced various anti-cancer effects, such as decreased cell proliferation, migration, and invasion, as well as increased apoptosis. Furthermore, the overexpression of TAS2Rs resulted in a decreased tumour incidence in an in vivo study and TAS2R activation could even enhance the therapeutic effect of chemotherapeutics in vitro. Finally, higher expression levels of TAS2Rs in primary cancerous cells and tissues were associated with an improved prognosis in humans. Conclusion: Since current evidence demonstrates a functional role of TAS2Rs in carcinogenesis, further studies should exploit their potential as (co-)targets of chemotherapeutics.


Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3127
Author(s):  
Bianca Semplici ◽  
Francesca Paola Luongo ◽  
Sofia Passaponti ◽  
Claudia Landi ◽  
Laura Governini ◽  
...  

Bitter taste receptors (TAS2RS) expression is not restricted to the oral cavity and the presence of these receptors in the male reproductive system and sperm provides insights into their possible role in human reproduction. To elucidate the potential role of TAS2Rs in the female reproductive system, we investigated the expression and localization of bitter taste receptors and the components of signal transduction cascade involved in the pathway of taste receptors in somatic follicular cells obtained from women undergoing assisted reproductive techniques. We found that TAS2R genes are expressed in both cumulus (CCs) and granulosa (GCs) cells, with TAS2R14 being the most highly expressed bitter receptor subtype. Interestingly, a slight increase in the expression of TAS2R14 and TAS2R43 was shown in both GCs and CCs in young women (p < 0.05), while a negative correlation may be established between the number of oocytes collected at the pickup and the expression of TAS2R43. Regarding α-gustducin and α-transducin, two Gα subunits expressed in the taste buds on the tongue, we provide evidence for their expression in CCs and GCs, with α-gustducin showing two additional isoforms in GCs. Finally, we shed light on the possible downstream transduction pathway initiated by taste receptor activation in the female reproductive system. Our study, showing for the first time the expression of taste receptors in the somatic ovarian follicle cells, significantly extends the current knowledge of the biological role of TAS2Rs for human female fertility.


2020 ◽  
pp. jbc.RA120.016056
Author(s):  
Donghwa Kim ◽  
Maria Castaño ◽  
Lauren K Lujan ◽  
Jung A. Woo ◽  
Stephen B. Liggett

For most GPCRs, the third intracellular loops (IL3) and C-terminal tails (CT) are sites for GRK-mediated phosphorylation, leading to b-arrestin binding and agonist-specific desensitization. These regions of the G protein-coupled bitter taste receptors (TAS2Rs) are short compared to the superfamily, and their functional role is unclear. TAS2R14 expressed on human airway smooth muscle (HASM) cells relax the cell, suggesting a novel target for bronchodilators. To assess IL3 and CT in agonist-promoted TAS2R14 desensitization (tachyphylaxis), we generated GST-fusion proteins of both the WT sequence and Ala substituted for Ser/Thr in the IL3 and CT sequences. In vitro, activated GRK2 phosphorylated both WT IL3 and WT CT proteins but not Ala-substituted forms. Next, TAS2R14s with mutations in IL3 (IL-5A), CT (CT-5A) and in both regions (IL/CT-10A) were expressed in HEK-293T cells. IL/CT-10A and CT-5A failed to undergo desensitization of the [Ca2+]i response compared to WT, indicating functional desensitization by GRK-phosphorylation is at residues in the CT. Short-term desensitization of TAS2R14 was blocked by GRK2 knockdown in HASM cells. Receptor:b-arrestin binding was absent with IL/CT-10A and CT-5A, but was also reduced in IL-5A, indicating a role for IL3 phosphorylation in the b-arrestin interaction for this function. Agonist-promoted internalization of IL-5A and CT-5A receptors was impaired and these receptors failed to colocalize with early endosomes. These results show that agonist-promoted functional desensitization of TAS2R14 occurs by GRK phosphorylation of CT residues and b-arrestin binding. However, b-arrestin function in the internalization and trafficking of the receptor requires cooperative GRK phosphorylation of IL3 and CT residues.


2019 ◽  
Vol 369 (3) ◽  
pp. 466-472 ◽  
Author(s):  
Yumi Harada ◽  
Junichi Koseki ◽  
Hitomi Sekine ◽  
Naoki Fujitsuka ◽  
Hiroyuki Kobayashi

2021 ◽  
Vol 10 (4) ◽  
pp. 145
Author(s):  
MenizibeyaO Welcome ◽  
Abraham Jeremiah ◽  
DennisO Allagoa ◽  
Senol Dane ◽  
VladimirA Pereverzev

2015 ◽  
Vol 148 (4) ◽  
pp. S-343-S-344
Author(s):  
Ravinder Abrol ◽  
Susan Morvaridi ◽  
Hung Pham ◽  
Shuping S. Wu ◽  
Hongxiang Hui ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Gabriella Morini ◽  
Marcel Winnig ◽  
Timo Vennegeerts ◽  
Gigliola Borgonovo ◽  
Angela Bassoli

Vanilla is widely used in food preparation worldwide for its sensory properties, mainly related to its fragrance, being vanillin the major compound present in the processed vanilla. Vanillin is also known to elicit bitterness as a secondary sensory sensation, but the molecular mechanism of its bitterness has never been reported. Assay buffers of vanillin were tested in vitro on all known 25 human bitter taste receptors TAS2Rs. Three receptors, TAS2R14, TAS2R20, and TAS2R39, were activated, showing that these receptors are mediating the bitterness of vanillin. The result could be useful to improve the overall sensory profile of this broadly used food ingredient, but even more could represent the starting point for further studies to investigate the potential of vanillin in sensory nutrition and other pharmaceutical applications.


Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4572
Author(s):  
Gigliola Borgonovo ◽  
Nathan Zimbaldi ◽  
Marta Guarise ◽  
Floriana Bedussi ◽  
Marcel Winnig ◽  
...  

Sisymbrium officinale (L.) Scop., commonly known as “hedge mustard” or “the singer’s plant” is a wild plant common in Eurasian regions. Its cultivation is mainly dedicated to herboristic applications and it has only recently been introduced into Italy. The active botanicals in S. officinale are glucosinolates, generally estimated by using UV or high-performance liquid chromatography (HPLC). Using both techniques, we measured the total glucosinolates from S. officinale in different parts of the plant as roots, leaves, seeds, and flowers. A comparison was made for cultivated and wild samples, and for samples obtained with different pre-treatment and fresh, frozen, and dried storage conditions. Cultivated and wild plants have a comparable amount of total glucosinolates, while drying procedures can reduce the final glucosinolates content. The content in glucoputranjivin, which is the chemical marker for glucosinolates in S. officinale, has been determined using HPLC and a pure reference standard. Glucoputranjivin and two isothiocyanates from S. officinale have been submitted to in vitro assays with the platform of bitter taste receptors of the T2Rs family. The results show that glucoputranjivin is a selective agonist of receptor T2R16.


2021 ◽  
Vol 288 (1947) ◽  
Author(s):  
Florian Ziegler ◽  
Maik Behrens

The bitter taste sensation is important to warn mammals of the ingestion of potentially toxic food compounds. For mammals, whose nutrition relies on highly specific food sources, such as blood in the case of vampire bats, it is unknown if bitter sensing is involved in prey selection. By contrast to other bat species, vampire bats exhibit numerous bitter taste receptor pseudogenes, which could point to a decreased importance of bitter taste. However, electrophysiological and behavioural studies suggest the existence of functional bitter taste transmission. To determine the agonist spectra of the three bitter taste receptors that are conserved in all three vampire bat species, we investigated the in vitro activation of Desmodus rotundus T2R1, T2R4 and T2R7. Using a set of 57 natural and synthetic bitter compounds, we were able to identify agonists for all three receptors. Hence, we confirmed a persisting functionality and, consequently, a putative biological role of bitter taste receptors in vampire bats. Furthermore, the activation of the human TAS2R7 by metal ions is shown to be conserved in D. rotundus .


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