VirtuousPocketome: a computational tool for screening protein-ligand complexes to identify similar binding sites.

Protein residues within binding pockets play a critical role in determining the range of ligands that can interact with a protein, influencing its structure and function. Identifying structural similarities in proteins offers valuable insights into their function and activation mechanisms, aiding in predicting protein-ligand interactions, anticipating off-target effects, and facilitating the development of therapeutic agents. Numerous computational methods assessing global or local similarity in protein cavities have emerged, but their utilization is impeded by complexity, impractical automation for amino acid pattern searches, and an inability to evaluate the dynamics of scrutinized protein-ligand systems. Here, we present a general, automatic and unbiased computational pipeline, named VirtuousPocketome, aimed at screening huge databases of proteins for similar binding pockets starting from an interested protein-ligand complex. We demonstrate the pipeline's potential by exploring a recently-solved human bitter taste receptor, i.e. the TAS2R46, complexed with strychnine. We pinpointed 145 proteins sharing similar binding sites compared to the analysed bitter taste receptor and the enrichment analysis highlighted the related biological processes, molecular functions and cellular components. This work represents the foundation for future studies aimed at understanding the effective role of tastants outside the gustatory system: this could pave the way towards the rationalization of the diet as a supplement to standard pharmacological treatments and the design of novel tastants-inspired compounds to target other proteins involved in specific diseases or disorders. The proposed pipeline is publicly accessible, can be applied to any protein-ligand complex, and could be expanded to screen any database of protein structures.

A novel biomimetic electrochemical taste-biosensor based on conformational changes of the taste receptor.

Taste sensor, a useful tool which could detect and identify thousands of different chemical substances in liquid environments, has attracted continuous concern from beverage and foodstuff industry and its consumers. Although many taste sensing methods have been extensively developed, the assessment of tastant content remains challenging due to the limitations of sensor selectivity and sensitivity. Here we present a novel biomimetic electrochemical taste-biosensor based on bioactive sensing elements and immune amplification with nanomaterials carrier to address above concerns, while taking sweet taste perception as a model. The proposed biosensor based on ligand binding domain (T1R2 VFT) of human sweet taste receptor protein showed human mimicking character and initiated the application of immune recognition in gustation biosensor, which can precisely and sensitively distinguish sweet substances against other related gustation substances with detection limit of 5.1 pM, far less than that of taste sensors without immune amplification whose detection limit was 0.48 nM. The performance test demonstrated the biosensor has the capacity of monitoring the response of sweet substances in real food environments, which is crucial in practical. This biomimetic electrochemical taste-biosensor can work as a new screening platform for newly developed tastants and disclose sweet perception mechanism.

Bitter taste receptors in the reproductive system: Function and therapeutic implications.

Type 2 taste receptors (TAS2Rs), traditionally known for their role in bitter taste perception, are present in diverse reproductive tissues of both sexes. This review explores our current understanding of TAS2R functions with a particular focus on reproductive health. In males, TAS2Rs are believed to play potential roles in processes such as sperm chemotaxis and male fertility. Genetic insights from mouse models and human polymorphism studies provide some evidence for their contribution to male infertility. In female reproduction, it is speculated that TAS2Rs influence the ovarian milieu, shaping the functions of granulosa and cumulus cells and their interactions with oocytes. In the uterus, TAS2Rs contribute to uterine relaxation and hold potential as therapeutic targets for preventing preterm birth. In the placenta, they are proposed to function as vigilant sentinels, responding to infection and potentially modulating mechanisms of fetal protection. In the cervix and vagina, their analogous functions to those in other extraoral tissues suggest a potential role in infection defense. In addition, TAS2Rs exhibit altered expression patterns that profoundly affect cancer cell proliferation and apoptosis in reproductive cancers. Notably, TAS2R agonists show promise in inducing apoptosis and overcoming chemoresistance in these malignancies. Despite these advances, challenges remain, including a lack of genetic and functional studies. The application of techniques such as single-cell RNA sequencing and clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated endonuclease 9 gene editing could provide deeper insights into TAS2Rs in reproduction, paving the way for novel therapeutic strategies for reproductive disorders.

Putative role of endothelin receptor B in the development and maintenance of taste buds within the circumvallate papillae.

This study aimed to achieve a better understanding of taste receptor cell development relative to endothelin receptor B (ETB) in circumvallate papillae (CVP). ETB localization was assessed by immunohistochemistry during tongue development of the mouse. Co-localization of ETB with taste receptor type III cell marker, Synaptosomal-Associated Protein 25 kDa (SNAP25), was evident in both the developing and adult CVP. ETB was strongly localized in the stromal core region. As development progressed, ETB became localized in the CVP mesenchyme and partially in the epithelium. ETB and SNAP25 co-localization indicates that ETB may regulate innervation from the CVP mesenchyme to taste buds.

Effect of salivary gland removal on taste preference in mice.

To evaluate the effect of decreased salivary secretion on taste preference, we investigated taste preference for five basic tastes by a 48 h two-bottle preference test using a mouse model (desalivated mice) that underwent surgical removal of three major salivary glands: the parotid, submandibular, and sublingual glands. In the desalivated mice, the avoidance behaviors for bitter and salty tastes and the attractive behaviors for sweet and umami tastes were significantly decreased. We confirmed that saliva is necessary to maintain normal taste preference. To estimate the cause of the preference changes, we investigated the effects of salivary gland removal on the expression of taste-related molecules in the taste buds. No apparent changes were observed in the expression levels or patterns of taste-related molecules after salivary gland removal. When the protein concentration and composition in the saliva were compared between the control and desalivated mice, the protein concentration decreased and its composition changed after major salivary gland removal. These results suggest that changes in protein concentration and composition in the saliva may be one of the factors responsible for the changes in taste preferences observed in the desalivated mice.

Altered peripheral taste function in a mouse model of inflammatory bowel disease.

Increased sugar intake and taste dysfunction have been reported in patients with inflammatory bowel disease (IBD), a chronic disorder characterized by diarrhea, pain, weight loss and fatigue. It was previously unknown whether taste function changes in mouse models of IBD. Mice consumed dextran sodium sulfate (DSS) during three 7-day cycles to induce chronic colitis. DSS-treated mice displayed signs of disease, including significant weight loss, diarrhea, loss of colon architecture, and inflammation of the colon. After the last DSS cycle we assessed taste function by recording electrophysiological responses from the chorda tympani (CT) nerve, which transmits activity from lingual taste buds to the brain. DSS treatment significantly reduced neural taste responses to natural and artificial sweeteners. Responses to carbohydrate, salt, sour or bitter tastants were unaffected in mice with colitis, but umami responses were modestly elevated. DSS treatment modulated the expression of receptor subunits that transduce sweet and umami stimuli in oral taste buds as a substrate for functional changes. Dysregulated systemic cytokine responses or dysbiosis that occurs during chronic colitis may be upstream from changes in oral taste buds. We demonstrate for the first time that colitis alters taste input to the brain, which could exacerbate malnutrition in IBD patients.

Vimentin Localization in the Zebrafish Oral Cavity: A Potential Role in Taste Buds Regeneration.

The morphology of the oral cavity of fish is related to their feeding habits. In this context, taste buds are studied for their ability to catch chemical stimuli and their cell renewal capacity. Vimentin RV202 is a protein employed as a marker for mesenchymal cells that can differentiate along different lineages and to self-renew, while Calretinin N-18 is employed as a marker of sensory cells, and ubiquitin is a protein crucial for guiding the fate of stem cells throughout development. In this study, a surface morphology investigation and an immunohistochemical analysis have been conducted. The results of the present study reveal, for the first time, the presence of Vimentin RV202 in a taste bud cell population of zebrafish. Some taste bud cells are just Vimentin RV202-immunoreactive, while in other cells Vimentin RV202 and Calretinin N-18 colocalize. Some taste buds are just reactive to Calretinin N-18. Vimentin RV202-immunoreactive cells have been observed in the connective layer and in the basal portion of the taste buds. The immunoreactivity of ubiquitin was restricted to sensory cells. Further studies are needed to elucidate the role of Vimentin RV202 in the maturation of taste bud cells, its potential involvement in the regeneration of these chemosensory organs, and its eventual synergic work with ubiquitin.

Relevance of Phytochemical Taste for Anti-Cancer Activity: A Statistical Inquiry.

Targeting inflammation and the pathways linking inflammation with cancer is an innovative therapeutic strategy. Tastants are potential candidates for this approach, since taste receptors display various biological functions, including anti-inflammatory activity (AIA). The present study aims to explore the power different tastes have to predict a phytochemical's anti-cancer properties. It also investigates whether anti-inflammatory phytocompounds also have anti-cancer effects, and whether there are tastes that can better predict a phytochemical's bivalent biological activity. Data from the PlantMolecularTasteDB, containing a total of 1527 phytochemicals, were used. Out of these, only 624 phytocompounds met the inclusion criterion of having 40 hits in a PubMed search, using the name of the phytochemical as the keyword. Among them, 461 phytochemicals were found to possess anti-cancer activity (ACA). The AIA and ACA of phytochemicals were strongly correlated, irrespective of taste/orosensation or chemical class. Bitter taste was positively correlated with ACA, while sweet taste was negatively correlated. Among chemical classes, only flavonoids (which are most frequently bitter) had a positive association with both AIA and ACA, a finding confirming that taste has predictive primacy over chemical class. Therefore, bitter taste receptor agonists and sweet taste receptor antagonists may have a beneficial effect in slowing down the progression of inflammation to cancer.

Expression of taste sentinels, T1R, T2R, and PLCß2, on the passageway for olfactory signals in zebrafish.

The senses of taste and smell detect overlapping sets of chemical compounds in fish, e.g. amino acids are detected by both senses. However, so far taste and smell organs appeared morphologically to be very distinct, with a specialized olfactory epithelium for detection of odors and taste buds located in the oral cavity and lip for detection of tastants. Here, we report dense clusters of cells expressing T1R and T2R receptors as well as their signal transduction molecule PLCß2 in nostrils of zebrafish, i.e. on the entrance funnel through which odor molecules must pass to be detected by olfactory sensory neurons. Quantitative evaluation shows the density of these chemosensory cells in the nostrils to be as high or higher than that in the established taste organs oral cavity and lower lip. Hydrodynamic flow is maximal at the nostril rim enabling high throughput chemosensation in this organ. Taken together, our results suggest a sentinel function for these chemosensory cells in the nostril.

[Genetic variants in CD36: emerging role in oral fat perception and food preferences]. / Variantes genéticas en CD36: evidencia emergente en la percepción oral de las grasas y las preferencias alimentarias.

Introduction: CD36 is a receptor involved in physiologic, metabolic and pathologic processes. Due to its affinity for long-chain fatty acids, it has been postulated as a taste receptor of fatty taste. In this review, the emerging genetic evidence linking CD36 to oral fat perception is analyzed. A systematic literature search was conducted in PubMed, published articles from 2000 to 2022 were considered. Multiple studies have shown an association of some genetic variants in CD36 with fat foods preferences and it has been suggested that these variants can modify oral fat perception thresholds however the evidence is still heterogeneous; this can be explained by the genetic diversity of populations, the nutritional status and participant's characteristics, as well as other methodological aspects. Other factors involved in oral fat perception were and identified and discussed including the interaction with other flavors, hormones, and epigenetic factors. The conclusion is that the evidence supporting the role of CD36 as a dietary lipid receptor, the role of its genetic variants in fat acids oral perception thresholds and food preferences is intermediate level and more investigations are necessary in other populations with large number of participants as well as considering the interaction between different hormones and the expression of CD36.

Introducción: CD36 es un receptor involucrado en procesos fisiológicos, metabólicos y patológicos. Debido a su afinidad por ácidos grasos de cadena larga es uno de los principales receptores de lípidos provenientes de la dieta. En esta revisión se analiza la evidencia genética emergente que vincula a CD36 en la percepción oral de grasa. Se realizó una búsqueda sistemática en la base de datos PubMed considerando artículos publicados en el periodo 2000-2022. Múltiples estudios asocian a algunas variantes genéticas en CD36 con las preferencias por alimentos con contenido graso y se ha postulado que estas variantes pueden modificar los umbrales de percepción oral de grasas, sin embargo, la evidencia es heterogénea; esto puede ser explicado por la diversidad genética de las poblaciones, el estado nutricional y características de los participantes, así como a otros aspectos metodológicos. Se identificaron y se discuten otros factores implicados en la percepción oral de grasas, incluyendo la interacción con otros sabores, hormonas y factores epigenéticos. Se concluye que la evidencia que apoya el papel de CD36 como receptor de los lípidos provenientes de la dieta es intermedio y son necesarias más investigaciones en diversas poblaciones con un gran número de participantes, así como considerar la interacción entre distintas hormonas y la expresión de CD36.

Sweet Taste Receptors and Associated Sweet Peptides: Insights into Structure and Function.

Long-term consumption of a high-sugar diet may contribute to the pathogenesis of several chronic diseases, such as obesity and type 2 diabetes. Sweet peptides derived from a wide range of food sources can enhance sweet taste without compromising the sensory properties. Therefore, the research and application of sweet peptides are promising strategies for reducing sugar consumption. This work first outlined the necessity for global sugar reduction, followed by the introduction of sweet taste receptors and their associated transduction mechanisms. Subsequently, recent research progress in sweet peptides from different protein sources was summarized. Furthermore, the main methods for the preparation and evaluation of sweet peptides were presented. In addition, the current challenges and potential applications are also discussed. Sweet peptides can stimulate sweetness perception by binding sweet taste receptors T1R2 and T1R3 in taste buds, which is an effective strategy for reducing sugar consumption. At present, sweet peptides are mainly prepared artificially by synthesis, hydrolysis, microbial fermentation, and bioengineering strategies. Furthermore, sensory evaluation, electronic tongues, and cell models have been used to assess the sweet taste intensity. The present review can provide a theoretical reference for reducing sugar consumption with the aid of sweet peptides in the food industry.

Gene expression analyses of TAS1R taste receptors relevant to the treatment of cardiometabolic disease.

The sweet taste receptor (STR) is a G protein-coupled receptor (GPCR) responsible for mediating cellular responses to sweet stimuli. Early evidence suggests that elements of the STR signaling system are present beyond the tongue in metabolically active tissues, where it may act as an extraoral glucose sensor. This study aimed to delineate expression of the STR in extraoral tissues using publicly available RNA-sequencing repositories. Gene expression data was mined for all genes implicated in the structure and function of the STR, and control genes including highly expressed metabolic genes in relevant tissues, other GPCRs and effector G proteins with physiological roles in metabolism, and other GPCRs with expression exclusively outside the metabolic tissues. Since the physiological role of the STR in extraoral tissues is likely related to glucose sensing, expression was then examined in diseases related to glucose-sensing impairment such as type 2 diabetes. An aggregate co-expression network was then generated to precisely determine co-expression patterns among the STR genes in these tissues. We found that STR gene expression was negligible in human pancreatic and adipose tissues, and low in intestinal tissue. Genes encoding the STR did not show significant co-expression or connectivity with other functional genes in these tissues. In addition, STR expression was higher in mouse pancreatic and adipose tissues, and equivalent to human in intestinal tissue. Our results suggest that STR expression in mice is not representative of expression in humans, and the receptor is unlikely to be a promising extraoral target in human cardiometabolic disease.

Transient Receptor Potential Ankyrin 1 in Taste Nerve Contributes to the Sense of Sweet Taste in Mice.

Transient receptor potential (TRP) channels play a significant role in taste perception. TRP ankyrin 1 (TRPA1) is present in the afferent sensory neurons and is activated by food-derived ingredients, such as Japanese horseradish, cinnamon, and garlic. The present study aimed to investigate the expression of TRPA1 in taste buds, and determine its functional roles in taste perception using TRPA1-deficient mice. In circumvallate papillae, TRPA1 immunoreactivity colocalised with P2X2 receptor-positive taste nerves but not with type II or III taste cell markers. Behavioural studies showed that TRPA1 deficiency significantly reduced sensitivity to sweet and umami tastes, but not to salty, bitter, and sour tastes, compared to that in wild-type animals. Furthermore, administration of the TRPA1 antagonist HC030031 significantly decreased taste preference to sucrose solution compared to that in the vehicle-treated group in the two-bottle preference tests. TRPA1 deficiency did not affect the structure of circumvallate papillae or the expression of type II or III taste cell and taste nerve markers. Adenosine 5'-O-(3-thio)triphosphate evoked inward currents did not differ between P2X2- and P2X2/TRPA1-expressing human embryonic kidney 293T cells. TRPA1-deficient mice had significantly decreased c-fos expression in the nucleus of the solitary tract in the brain stem following sucrose stimulation than wild-type mice. Taken together, the current study suggested that TRPA1 in the taste nerve contributes to the sense of sweet taste in mice.

Adrenomedullin Enhances Mouse Gustatory Nerve Responses to Sugars via T1R-Independent Sweet Taste Pathway.

On the tongue, the T1R-independent pathway (comprising glucose transporters, including sodium-glucose cotransporter (SGLT1) and the KATP channel) detects only sugars, whereas the T1R-dependent (T1R2/T1R3) pathway can broadly sense various sweeteners. Cephalic-phase insulin release, a rapid release of insulin induced by sensory signals in the head after food-related stimuli, reportedly depends on the T1R-independent pathway, and the competitive sweet taste modulators leptin and endocannabinoids may function on these two different sweet taste pathways independently, suggesting independent roles of two oral sugar-detecting pathways in food intake. Here, we examined the effect of adrenomedullin (ADM), a multifunctional regulatory peptide, on sugar sensing in mice since it affects the expression of SGLT1 in rat enterocytes. We found that ADM receptor components were expressed in T1R3-positive taste cells. Analyses of chorda tympani (CT) nerve responses revealed that ADM enhanced responses to sugars but not to artificial sweeteners and other tastants. Moreover, ADM increased the apical uptake of a fluorescent D-glucose derivative into taste cells and SGLT1 mRNA expression in taste buds. These results suggest that the T1R-independent sweet taste pathway in mouse taste cells is a peripheral target of ADM, and the specific enhancement of gustatory nerve responses to sugars by ADM may contribute to caloric sensing and food intake.

Regeneration of taste through sonic hedgehog upregulation by photobiomodulation.

This study investigated photobiomodulation (PBM) effects in Sonic hedgehog (Shh) signaling as a potential approach to taste preservation and regeneration. Primary taste cell (TC) cultures were treated with Shh antagonist vismodegib and irradiated using a continuous wave type 630 nm light-emitting diode (10 mW/cm2 ) array, with single or multiple doses of 30 J/cm2 to determine dose inducing significant upregulation effect. Shh, Ptch, Smo, and Gli1 were significantly upregulated at 120 J/cm2 , used as the minimum dose in vivo. Vismodegib was administered via daily oral gavage for 21 days (30 mg/kg) to induce Shh inhibition in the tongue of rat animal models resulting in taste bud damage and taste dysfunction. PBM treatment using a 630 nm laser (3 W/cm2 ) at a radiant exposure of 120 J/cm2 (24 J/cm2 × 5) successfully upregulated the Shh protein expression, regenerated taste buds, and recovered taste function.

Electronic cigarettes can damage lingual papillae and taste buds. Can vitamins C and E supplementation reverse this damage?

AIMS: This histological study focuses on the impact of electronic cigarette liquid (EC) on lingual papillae, especially taste buds, compare it to nicotine, and investigates the potential of vitamins in reversing these unwanted changes. MAIN METHODS: 40 adult male rats were allocated into 5 groups. Control injected saline intraperitoneally, electronic cigarettes group injected EC-liquid containing nicotine of dose (0.75 mg/kg), electronic cigarette group injected EC-liquid then supplemented orally with vitamins C and E, nicotine group injected pure nicotine of dose (0.75 mg/kg) and lastly nicotine group injected with pure nicotine of dose (0.75 mg/kg) then supplemented orally with vitamins C and E. Keratin surface area and the ratio between taste buds and its epithelial covering surface areas in fungiform papillae were measured. KEY FINDINGS: Histological examination of EC group revealed abnormal epithelial stratification and mitotic figs. EC plus V group showed intact basal cell layer. N group showed better histological stratification than EC group. Fungiform and circumvallate papillae in EC and N groups showed distorted appearance of taste buds. Histomorphometry analysis showed a significant decrease in taste buds to epithelium surface areas in EC, nicotine, and EC plus V groups, p-value (<0.05). There was no significant difference between control and N plus V groups. SIGNIFICANCE: Administration of vitamins C and E showed preservation of normal histological features of the lingual mucous membrane. EC caused striking damage to taste buds even after the administration of vitamins. The negative effects of electronic cigarettes are not confined only to the presence of nicotine.

Effects of temperature on action potentials and ion conductances in type II taste-bud cells.

Temperature strongly influences the intensity of taste, but it remains understudied despite its physiological, hedonic, and commercial implications. The relative roles of the peripheral gustatory and somatosensory systems innervating the oral cavity in mediating thermal effects on taste sensation and perception are poorly understood. Type II taste-bud cells, responsible for sensing sweet, bitter umami, and appetitive NaCl, release neurotransmitters to gustatory neurons by the generation of action potentials, but the effects of temperature on action potentials and the underlying voltage-gated conductances are unknown. Here, we used patch-clamp electrophysiology to explore the effects of temperature on acutely isolated type II taste-bud cell electrical excitability and whole cell conductances. Our data reveal that temperature strongly affects action potential generation, properties, and frequency and suggest that thermal sensitivities of underlying voltage-gated Na+ and K+ channel conductances provide a mechanism for how and whether voltage-gated Na+ and K+ channels in the peripheral gustatory system contribute to the influence of temperature on taste sensitivity and perception.NEW & NOTEWORTHY The temperature of food affects how it tastes. Nevertheless, the mechanisms involved are not well understood, particularly whether the physiology of taste-bud cells in the mouth is involved. Here we show that the electrical activity of type II taste-bud cells that sense sweet, bitter, and umami substances is strongly influenced by temperature. These results suggest a mechanism for the influence of temperature on the intensity of taste perception that resides in taste buds themselves.

Cisplatin attenuates taste cell homeostasis and induces inflammatory activation in the circumvallate papilla.

Rationale: Gustation is important to several biological functions in mammals. However, chemotherapy drugs often harm taste perception in cancer patients, while the underlying mechanism is still unclear for most drugs and there is no effective way to restore taste function. This study investigated the effects of cisplatin on the taste cell homeostasis and gustatory function. Methods: We used both mice and taste organoid models to study the effect of cisplatin on taste buds. Gustometer assay, gustatory nerve recording, RNA-Sequencing, quantitative PCR, and immunohistochemistry was performed to analyze the cisplatin-induced alteration in taste behavior and function, transcriptome, apoptosis, cell proliferation and taste cell generation. Results: Cisplatin inhibited proliferation and promoted apoptosis in the circumvallate papilla, leading to significant impairment in taste function and receptor cell generation. The transcriptional profile of genes associated with cell cycle, metabolic process and inflammatory response was significantly altered after cisplatin treatment. Cisplatin inhibited growth, promoted apoptosis, and deferred taste receptor cell differentiation in taste organoids. LY411575, a γ-secretase inhibitor, reduced the number of apoptotic cells and increased the number of proliferative cells and taste receptor cells, potentially suggesting as a taste tissue protective agent against chemotherapy. LY411575 treatment could offset the increased number of Pax1+ or Pycr1+ cells induced by cisplatin in the circumvallate papilla and taste organoids. Conclusion: This study highlights the inhibitory effects of cisplatin on taste cell homeostasis and function, identifies critical genes and biological processes regulated by chemotherapy, and proposes potential therapeutic targets and strategy for taste dysfunction in cancer patients.

In Vitro Functional Characterization of Type-I Taste Bud Cells as Monocytes/Macrophages-like Which Secrete Proinflammatory Cytokines.

The sense of taste determines the choice of nutrients and food intake and, consequently, influences feeding behaviors. The taste papillae are primarily composed of three types of taste bud cells (TBC), i.e., type I, type II, and type III. The type I TBC, expressing GLAST (glutamate--aspartate transporter), have been termed as glial-like cells. We hypothesized that these cells could play a role in taste bud immunity as glial cells do in the brain. We purified type I TBC, expressing F4/80, a specific marker of macrophages, from mouse fungiform taste papillae. The purified cells also express CD11b, CD11c, and CD64, generally expressed by glial cells and macrophages. We further assessed whether mouse type I TBC can be polarized toward M1 or M2 macrophages in inflammatory states like lipopolysaccharide (LPS)-triggered inflammation or obesity, known to be associated with low-grade inflammation. Indeed, LPS-treatment and obesity state increased TNFα, IL-1ß, and IL-6 expression, both at mRNA and protein levels, in type I TBC. Conversely, purified type I TBC treated with IL-4 showed a significant increase in arginase 1 and IL-4. These findings provide evidence that type I gustatory cells share many features with macrophages and may be involved in oral inflammation.

Volatile Short-Chain Aliphatic Aldehydes Act as Taste Modulators through the Orally Expressed Calcium-Sensing Receptor CaSR.

Aldehydes are natural volatile aroma compounds generated by the Maillard reaction of sugars and amino acids in food and affect the flavor of food. They have been reported to exert taste-modifying effects, such as increases in taste intensity at concentrations below the odor detection threshold. The present study examined the taste-enhancing effects of short-chain aliphatic aldehydes, such as isovaleraldehyde (IVAH) and 2-methylbutyraldehyde, thus attempting to identify the taste receptors involved. The results obtained revealed that IVAH enhanced the taste intensity of taste solutions even under the condition of olfactory deprivation by a noseclip. Furthermore, IVAH activated the calcium-sensing receptor CaSR in vitro. Receptor assays on aldehyde analogues showed that C3-C6 aliphatic aldehydes and methional, a C4 sulfur aldehyde, activated CaSR. These aldehydes functioned as a positive allosteric modulator for CaSR. The relationship between the activation of CaSR and taste-modifying effects was investigated by a sensory evaluation. Taste-modifying effects were found to be dependent on the activation state of CaSR. Collectively, these results suggest that short-chain aliphatic aldehydes function as taste modulators that modify sensations by activating orally expressed CaSR. We propose that volatile aroma aldehydes may also partially contribute to the taste-modifying effect via the same molecular mechanism as kokumi substances.