scholarly journals An update on extra-oral bitter taste receptors

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tuzim Kamila ◽  
Korolczuk Agnieszka
Keyword(s):  
Bitter Taste ◽  
Therapeutic Potential ◽  
Taste Receptor ◽  
Taste Bud ◽  
Sensory Receptor ◽  
Ligand Selectivity ◽  
Physiological Processes ◽  
Health And Disease ◽  
Receptor Biology ◽  
G Protein Coupled

AbstractBitter taste-sensing type 2 receptors (TAS2Rs or T2Rs), belonging to the subgroup of family A G-protein coupled receptors (GPCRs), are of crucial importance in the perception of bitterness. Although in the first instance, TAS2Rs were considered to be exclusively distributed in the apical microvilli of taste bud cells, numerous studies have detected these sensory receptor proteins in several extra-oral tissues, such as in pancreatic or ovarian tissues, as well as in their corresponding malignancies. Critical points of extra-oral TAS2Rs biology, such as their structure, roles, signaling transduction pathways, extensive mutational polymorphism, and molecular evolution, have been currently broadly studied. The TAS2R cascade, for instance, has been recently considered to be a pivotal modulator of a number of (patho)physiological processes, including adipogenesis or carcinogenesis. The latest advances in taste receptor biology further raise the possibility of utilizing TAS2Rs as a therapeutic target or as an informative index to predict treatment responses in various disorders. Thus, the focus of this review is to provide an update on the expression and molecular basis of TAS2Rs functions in distinct extra-oral tissues in health and disease. We shall also discuss the therapeutic potential of novel TAS2Rs targets, which are appealing due to their ligand selectivity, expression pattern, or pharmacological profiles.

Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b and A3 Adenosine Receptors

2019 ◽  
Vol 25 (26) ◽  
pp. 2892-2905 ◽  
Author(s):  
Sumit Jamwal ◽  
Ashish Mittal ◽  
Puneet Kumar ◽  
Dana M. Alhayani ◽  
Amal Al-Aboudi
Keyword(s):  
Nervous System ◽  
Therapeutic Potential ◽  
The Body ◽  
Membrane Receptors ◽  
Physiological Importance ◽  
Physiological Processes ◽  
Central Nervous Systems ◽  
Energy Consuming ◽  
Metabolic Dysfunctions ◽  
G Protein Coupled

Adenosine is a naturally occurring nucleoside and an essential component of the energy production and utilization systems of the body. Adenosine is formed by the degradation of adenosine-triphosphate (ATP) during energy-consuming processes. Adenosine regulates numerous physiological processes through activation of four subtypes of G-protein coupled membrane receptors viz. A1, A2A, A2B and A3. Its physiological importance depends on the affinity of these receptors and the extracellular concentrations reached. ATP acts as a neurotransmitter in both peripheral and central nervous systems. In the peripheral nervous system, ATP is involved in chemical transmission in sensory and autonomic ganglia, whereas in central nervous system, ATP, released from synaptic terminals, induces fast excitatory postsynaptic currents. ATP provides the energetics for all muscle movements, heart beats, nerve signals and chemical reactions inside the body. Adenosine has been traditionally considered an inhibitor of neuronal activity and a regulator of cerebral blood flow. Since adenosine is neuroprotective against excitotoxic and metabolic dysfunctions observed in neurological and ocular diseases, the search for adenosinerelated drugs regulating adenosine transporters and receptors can be important for advancement of therapeutic strategies against these diseases. This review will summarize the therapeutic potential and recent SAR and pharmacology of adenosine and its receptor agonists and antagonists.

A kinetic study of bitter taste receptor sensing using immobilized porcine taste bud tissues

2017 ◽  
Vol 92 ◽  
pp. 74-80 ◽  
Author(s):  
Lihui Wei ◽  
Lixin Qiao ◽  
Guangchang Pang ◽  
Junbo Xie
Keyword(s):  
Kinetic Study ◽  
Bitter Taste ◽  
Taste Receptor ◽  
Taste Bud ◽  
Bitter Taste Receptor

scholarly journals Taste receptor polymorphisms and longevity: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Danilo Di Bona ◽  
Alberto Malovini ◽  
Giulia Accardi ◽  
Anna Aiello ◽  
Giuseppina Candore ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bitter Taste ◽  
Meta Analysis ◽  
Taste Receptor ◽  
The Other ◽  
Analytic Approach ◽  
Taste Receptors ◽  
South Italy ◽  
Physiological Processes ◽  
Different Populations

AbstractBitter taste receptors (TAS2R) are involved in a variety of non-tasting physiological processes, including immune-inflammatory ones. Therefore, their genetic variations might influence various traits. In particular, in different populations of South Italy (Calabria, Cilento, and Sardinia), polymorphisms of TAS2R16 and TAS238 have been analysed in association with longevity with inconsistent results. A meta-analytic approach to quantitatively synthesize the possible effect of the previous variants and, possibly, to reconcile the inconsistencies has been used in the present paper. TAS2R38 variants in the Cilento population were also analysed for their possible association with longevity and the obtained data have been included in the relative meta-analysis. In population from Cilento no association was found between TAS2R38 and longevity, and no association was observed as well, performing the meta-analysis with data of the other studies. Concerning TAS2R16 gene, instead, the genotype associated with longevity in the Calabria population maintained its significance in the meta-analysis with data from Cilento population, that, alone, were not significant in the previously published study. In conclusion, our results suggest that TAS2R16 genotype variant is associated with longevity in South Italy.

scholarly journals Functional characterization of the TAS2R38 bitter taste receptor for phenylthiocarbamide in colobine monkeys

2017 ◽  
Vol 13 (1) ◽  
pp. 20160834 ◽  
Author(s):  
Laurentia Henrieta Permita Sari Purba ◽  
Kanthi Arum Widayati ◽  
Kei Tsutsui ◽  
Nami Suzuki-Hashido ◽  
Takashi Hayakawa ◽  
...  
Keyword(s):  
Bitter Taste ◽  
Functional Characterization ◽  
Taste Receptor ◽  
Synonymous Mutations ◽  
Natural Toxins ◽  
Colobine Monkeys ◽  
Functional Analyses ◽  
G Protein Coupled

Bitterness perception in mammals is mostly directed at natural toxins that induce innate avoidance behaviours. Bitter taste is mediated by the G protein-coupled receptor TAS2R, which is located in taste cell membranes. One of the best-studied bitter taste receptors is TAS2R38, which recognizes phenylthiocarbamide (PTC). Here we investigate the sensitivities of TAS2R38 receptors to PTC in four species of leaf-eating monkeys (subfamily Colobinae). Compared with macaque monkeys (subfamily Cercopithecinae), colobines have lower sensitivities to PTC in behavioural and in vitro functional analyses. We identified four non-synonymous mutations in colobine TAS2R38 that are responsible for the decreased sensitivity of the TAS2R38 receptor to PTC observed in colobines compared with macaques. These results suggest that tolerance to bitterness in colobines evolved from an ancestor that was sensitive to bitterness as an adaptation to eating leaves.

scholarly journals Emerging Roles of RNA 3′-end Cleavage and Polyadenylation in Pathogenesis, Diagnosis and Therapy of Human Disorders

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 915 ◽  
Author(s):  
Jamie Nourse ◽  
Stefano Spada ◽  
Sven Danckwardt
Keyword(s):  
Rna Processing ◽  
Therapeutic Potential ◽  
Protein Complexes ◽  
Alternative Polyadenylation ◽  
Rna Motifs ◽  
Physiological Processes ◽  
Human Disorders ◽  
Tightly Coupled ◽  
Cleavage And Polyadenylation ◽  
Health And Disease

A crucial feature of gene expression involves RNA processing to produce 3′ ends through a process termed 3′ end cleavage and polyadenylation (CPA). This ensures the nascent RNA molecule can exit the nucleus and be translated to ultimately give rise to a protein which can execute a function. Further, alternative polyadenylation (APA) can produce distinct transcript isoforms, profoundly expanding the complexity of the transcriptome. CPA is carried out by multi-component protein complexes interacting with multiple RNA motifs and is tightly coupled to transcription, other steps of RNA processing, and even epigenetic modifications. CPA and APA contribute to the maintenance of a multitude of diverse physiological processes. It is therefore not surprising that disruptions of CPA and APA can lead to devastating disorders. Here, we review potential CPA and APA mechanisms involving both loss and gain of function that can have tremendous impacts on health and disease. Ultimately we highlight the emerging diagnostic and therapeutic potential CPA and APA offer.

scholarly journals Infection by the parasitic helminthTrichinella spiralisactivates a Tas2r-mediated signaling pathway in intestinal tuft cells

2019 ◽  
Vol 116 (12) ◽  
pp. 5564-5569 ◽  
Author(s):  
Xiao-Cui Luo ◽  
Zhen-Huang Chen ◽  
Jian-Bo Xue ◽  
Dong-Xiao Zhao ◽  
Chen Lu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
G Protein ◽  
Molecular Mechanisms ◽  
Bitter Taste ◽  
Trichinella Spiralis ◽  
Taste Receptor ◽  
Taste Bud ◽  
Tuft Cell ◽  
Tuft Cells

The parasitic helminthTrichinella spiralis, which poses a serious health risk to animals and humans, can be found worldwide. Recent findings indicate that a rare type of gut epithelial cell, tuft cells, can detect the helminth, triggering type 2 immune responses. However, the underlying molecular mechanisms remain to be fully understood. Here we show that both excretory–secretory products (E–S) and extract ofT. spiraliscan stimulate the release of the cytokine interleukin 25 (IL-25) from the mouse small intestinal villi and evoke calcium responses from tuft cells in the intestinal organoids, which can be blocked by a bitter-taste receptor inhibitor, allyl isothiocyanate. Heterologously expressed mouse Tas2r bitter-taste receptors, the expression of which is augmented during tuft-cell hyperplasia, can respond to the E–S and extract as well as to the bitter compound salicin whereas salicin in turn can induce IL-25 release from tuft cells. Furthermore, abolishment of the G-protein γ13 subunit, application of the inhibitors for G-protein αo/i, Gβγ subunits, and phospholipase Cβ2 dramatically reduces the IL-25 release. Finally, tuft cells are found to utilize the inositol triphosphate receptor type 2 (Ip3r2) to regulate cytosolic calcium and thus Trpm5 activity, while potentiation of Trpm5 by a sweet-tasting compound, stevioside, enhances tuft cell IL-25 release and hyperplasia in vivo. Taken together,T. spiralisinfection activates a signaling pathway in intestinal tuft cells similar to that of taste-bud cells, but with some key differences, to initiate type 2 immunity.

scholarly journals An Autonomous Cannabinoid System in Islets of Langerhans

2021 ◽  
Vol 12 ◽  
Author(s):  
Kanikkai Raja Aseer ◽  
Josephine M. Egan
Keyword(s):  
Insulin Secretion ◽  
Therapeutic Potential ◽  
Cell Damage ◽  
Cell Types ◽  
Β Cells ◽  
Β Cell ◽  
Glucose And Lipid Metabolism ◽  
Physiological Processes ◽  
Islet Physiology ◽  
G Protein Coupled

While endocannabinoids (ECs) and cannabis were primarily studied for their nervous system effects, it is now clear that ECs are also produced in the periphery where they regulate several physiological processes, including energy storage, glucose and lipid metabolism, insulin secretion and synthesis, and hepatocyte function. Within islet of Langerhans there is an autonomous EC system (ECS). Beta (β)-cells contain all the enzymes necessary for EC synthesis and degradation; ECs are generated in response to cellular depolarization; their paracrine influence on β-cells is mostly through the cannabinoid 1 receptor (CB1R) that is present on all β-cells; they modulate basal and glucose- and incretin-induced insulin secretion, and β-cell responses to various stressors. Furthermore, there is now accumulating evidence from preclinical studies that the autonomous islet ECS is a key player in obesity-induced inflammation in islets, and β-cell damage and apoptosis from many causes can be mitigated by CB1R blockers. We will thoroughly review the literature relevant to the effects of ECs and their receptors on β-cells and the other cell types within islets. Therapeutic potential of agents targeting EC/CB1R and CB2R is highly relevant because the receptors belong to the druggable G protein-coupled receptor superfamily. Present research in the ECS must be considered preliminary, especially with regards to human islet physiology, and further research is needed in order to translate basic cellular findings into clinical practice and the use of safe, clinically approved CBR modulators with and without glucose lowering combinations presently in therapeutic use for diabetes and obesity needs to be studied.

scholarly journals Chemical modification of neuropeptide Y for human Y1 receptor targeting in health and disease

2019 ◽  
Vol 400 (3) ◽  
pp. 299-311 ◽  
Author(s):  
Sven Hofmann ◽  
Kathrin Bellmann-Sickert ◽  
Annette G. Beck-Sickinger
Keyword(s):  
Neuropeptide Y ◽  
Peptide Yy ◽  
Peptide Hormone ◽  
Receptor Subtypes ◽  
Innovative Strategies ◽  
Y1 Receptor ◽  
Physiological Processes ◽  
Health And Disease ◽  
Innovative Drugs ◽  
G Protein Coupled

AbstractAs a very abundant neuropeptide in the brain and widely distributed peptide hormone in the periphery, neuropeptide Y (NPY) appears to be a multisignaling key peptide. Together with peptide YY, pancreatic polypeptide and the four human G protein-coupled receptor subtypes hY1R, hY2R, hY4R and hY5R it forms the NPY/hYR multiligand/multireceptor system, which is involved in essential physiological processes as well as in human diseases. In particular, NPY-induced hY1R signaling plays a central role in the regulation of food intake and stress response as well as in obesity, mood disorders and cancer. Thus, several hY1R-preferring NPY analogs have been developed as versatile tools to unravel the complex NPY/hY1R signaling in health and disease. Further, these peptides provide basic lead structures for the development of innovative drugs. Here, the current research is summarized focusing on the development of differently sized hY1R-preferring NPY analogs as well as their advances with respect to hY1R profiling, potential therapeutic applications and targeted cancer imaging and therapy. Finally, major limitations and innovative strategies for next generation hY1R-preferring NPY analogs are addressed.

scholarly journals Do Gut Microbes Taste?

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2581
Author(s):  
Ryan Leung ◽  
Mihai Covasa
Keyword(s):  
Taste Receptor ◽  
Taste Preference ◽  
Receptor Expression ◽  
Ingestive Behavior ◽  
Taste Perception ◽  
Intestinal Dysbiosis ◽  
Health And Disease ◽  
Short And Long Term ◽  
G Protein Coupled

Gut microbiota has emerged as a major metabolically active organ with critical functions in both health and disease. The trillions of microorganisms hosted by the gastrointestinal tract are involved in numerous physiological and metabolic processes including modulation of appetite and regulation of energy in the host spanning from periphery to the brain. Indeed, bacteria and their metabolic byproducts are working in concert with the host chemosensory signaling pathways to affect both short- and long-term ingestive behavior. Sensing of nutrients and taste by specialized G protein-coupled receptor cells is important in transmitting food-related signals, optimizing nutrition as well as in prevention and treatment of several diseases, notably obesity, diabetes and associated metabolic disorders. Further, bacteria metabolites interact with specialized receptors cells expressed by gut epithelium leading to taste and appetite response changes to nutrients. This review describes recent advances on the role of gut bacteria in taste perception and functions. It further discusses how intestinal dysbiosis characteristic of several pathological conditions may alter and modulate taste preference and food consumption via changes in taste receptor expression.

scholarly journals Update on GPCR-based targets for the development of novel antidepressants

2021 ◽  
Author(s):  
Ioannis Mantas ◽  
Marcus Saarinen ◽  
Zhi-Qing David Xu ◽  
Per Svenningsson
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
G Protein ◽  
Therapeutic Potential ◽  
G Protein Coupled Receptors ◽  
Major Depressive ◽  
Ligand Selectivity ◽  
Direct Targeting ◽  
Atypical Antidepressants ◽  
G Protein Coupled

AbstractTraditional antidepressants largely interfere with monoaminergic transport or degradation systems, taking several weeks to have their therapeutic actions. Moreover, a large proportion of depressed patients are resistant to these therapies. Several atypical antidepressants have been developed which interact with G protein coupled receptors (GPCRs) instead, as direct targeting of receptors may achieve more efficacious and faster antidepressant actions. The focus of this review is to provide an update on how distinct GPCRs mediate antidepressant actions and discuss recent insights into how GPCRs regulate the pathophysiology of Major Depressive Disorder (MDD). We also discuss the therapeutic potential of novel GPCR targets, which are appealing due to their ligand selectivity, expression pattern, or pharmacological profiles. Finally, we highlight recent advances in understanding GPCR pharmacology and structure, and how they may provide new avenues for drug development.

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