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1.
Biochem Biophys Res Commun ; 722: 150143, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38795451

ABSTRACT

Nuclear factor (NF)-κB signaling is not only important for the immune and inflammatory responses but also for the normal development of epithelial cells, such as those in the skin and tooth. Here, we generated epithelial cell-specific p65-deficient (p65Δepi-/-) mice to analyze the roles of NF-κB signaling in epithelial cell developent. Notably, p65Δepi-/- mice exhibited no abnormalities in their appearance compared to the control (p65flox/flox) littermates. Furthermore, no major changes were observed in the skin, hair growth, and shape and color of the incisors and molars. However, 65 % of p65Δepi-/- mice exhibited corneal thickening after 8 weeks of age, and 30 % of p65Δepi-/- mice exhibited hair growth from the mandibular incisors around 24 weeks of age. No hair growth was observed at 36 and 42 weeks of age. However, micro-computed tomography images revealed a large cavity below the mandibular incisors extending to the root of the incisor. Histological analysis revealed that the cavity was occupied by a connective tissue containing hair-like structures with many dark brown granules that disappeared after melanin bleaching, confirming the presence of hair. Although inflammatory cells were also observed near the eruption site of the incisor teeth of p65Δepi-/- mice, no major disturbance was observed in the arrangement of enamel epithelial cells. Overall, these results highlight the role of p65 in the maintenance of epithelial cell homeostasis during aging.

2.
Auris Nasus Larynx ; 51(3): 443-449, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38520975

ABSTRACT

OBJECTIVE: Olfactory and gustatory functions are important sensory aspects in humans. Although they are believed to influence each other, their interrelationship is not well understood. In this study, we aimed to investigate the relationship between the olfactory and gustatory functions based on the results of a large-scale epidemiological study (Iwaki Health Promotion Project) of the general local population. METHODS: We analyzed 565 participants who underwent taste and olfactory tests in the 2019 Iwaki Project. Gustatory function was tested for four taste qualities (sweet, sour, salty, and bitter) using whole-mouth taste tests. Olfactory function was tested using the University of Pennsylvania Smell Identification Test modified for Japanese (UPSIT-J). We evaluated sex-related differences between olfactory and gustatory functions and the effects of various factors on olfactory identification using multivariate analysis. Furthermore, we compared the percentage of accurate UPSIT-J responses between the normal and hypogeusia groups. We also analyzed the effects of taste and olfactory functions on eating. RESULTS: Olfactory and gustatory functions were lower in men than in women. Among the four taste qualities, salty taste was the most closely associated with olfactory identification ability, with lower olfactory scores of salty taste in the hypogeusia group than in the normal group. Moreover, the hyposmia group had higher daily salt intake than the normal olfaction group in women. CONCLUSION: These results suggest that olfactory identification tests may be useful in predicting elevated salt cognitive thresholds, leading to a reduction in salt intake, which may contribute to hypertension prevention.


Subject(s)
Health Promotion , Humans , Male , Female , Middle Aged , Adult , Japan/epidemiology , Aged , Sex Factors , Smell/physiology , Taste/physiology , Ageusia/physiopathology , Ageusia/epidemiology , Olfaction Disorders/epidemiology , Anosmia/physiopathology , Taste Perception/physiology
3.
eNeuro ; 10(9)2023 09.
Article in English | MEDLINE | ID: mdl-37696662

ABSTRACT

Drug-induced taste disorders reduce quality of life, but little is known about the molecular mechanisms by which drugs induce taste disturbances. In this study, we investigated the short-term and long-term effects of the antiarrhythmic drug flecainide, which is known to cause taste dysfunction. Analyses of behavioral responses (licking tests) revealed that mice given a single intraperitoneal injection of flecainide exhibited a significant reduction in preference for a sour tastant (HCl) but not for other taste solutions (NaCl, quinine, sucrose, KCl and monopotassium glutamate) when compared with controls. Mice administered a single dose of flecainide also had significantly higher taste nerve responses to HCl but not to other taste solutions. Compared with controls, mice administered flecainide once-daily for 30 d showed a reduced preference for HCl without any changes in the behavioral responses to other taste solutions. The electrophysiological experiments using HEK293T cells transiently expressing otopetrin-1 (Otop1; the mouse sour taste receptor) showed that flecainide did not alter the responses to HCl. Taken together, our results suggest that flecainide specifically enhances the response to HCl in mice during short-term and long-term administration. Although further studies will be needed to elucidate the molecular mechanisms, these findings provide new insights into the pathophysiology of drug-induced taste disorders.


Subject(s)
Anti-Arrhythmia Agents , Flecainide , Humans , Animals , Mice , Anti-Arrhythmia Agents/pharmacology , Flecainide/pharmacology , HEK293 Cells , Quality of Life , Taste Disorders , Membrane Proteins
4.
FEBS Lett ; 597(15): 2006-2016, 2023 08.
Article in English | MEDLINE | ID: mdl-37418589

ABSTRACT

GPRC5C is an orphan G protein-coupled receptor (GPCR) that belongs to the class C GPCR family. Although GPRC5C is expressed in various organs, its function and ligand are still undetermined. We found that GPRC5C is expressed in mouse taste cells, enterocytes, and pancreatic α-cells. In functional imaging assays, HEK293 cells heterologously expressing GPRC5C and the chimeric G protein α subunit Gα16-gust44 showed robust intracellular Ca2+ increases in response to monosaccharides, disaccharides, and a sugar alcohol, but not an artificial sweetener or sweet-tasting amino acid. Notably, Ca2+ increases occurred after washout, not during stimulation. Our findings suggest that GPRC5C has receptor properties which lead to novel 'off' responses to saccharide detachment and may work as an internal or external chemosensor specifically tuned to natural sugars.


Subject(s)
Disaccharides , Receptors, G-Protein-Coupled , Animals , Humans , Mice , HEK293 Cells , Ligands , Receptors, G-Protein-Coupled/metabolism
5.
Commun Biol ; 6(1): 340, 2023 04 03.
Article in English | MEDLINE | ID: mdl-37012338

ABSTRACT

The sweet taste receptor plays an essential role as an energy sensor by detecting carbohydrates. However, the dynamic mechanisms of receptor activation remain unclear. Here, we describe the interactions between the transmembrane domain of the G protein-coupled sweet receptor subunit, TAS1R3, and allosteric modulators. Molecular dynamics simulations reproduced species-specific sensitivity to ligands. We found that a human-specific sweetener, cyclamate, interacted with the mouse receptor as a negative allosteric modulator. Agonist-induced allostery during receptor activation was found to destabilize the intracellular part of the receptor, which potentially interfaces with the Gα subunit, through ionic lock opening. A common human variant (R757C) of the TAS1R3 exhibited a reduced response to sweet taste, in support of our predictions. Furthermore, histidine residues in the binding site acted as pH-sensitive microswitches to modulate the sensitivity to saccharin. This study provides important insights that may facilitate the prediction of dynamic activation mechanisms for other G protein-coupled receptors.


Subject(s)
Receptors, G-Protein-Coupled , Taste , Mice , Humans , Animals , Taste/physiology , Receptors, G-Protein-Coupled/metabolism , Binding Sites , Protein Domains , Cyclamates
6.
Front Cell Neurosci ; 17: 1279059, 2023.
Article in English | MEDLINE | ID: mdl-38164437

ABSTRACT

Drug-induced taste disorders are a serious problem in an aging society. This study investigated the mechanisms underlying taste disturbances induced by diclofenac, a non-steroidal anti-inflammatory drug that reduces pain and inflammation by inhibiting the synthesis of prostaglandins by cyclooxygenase enzymes (COX-1 and COX-2). RT-PCR analyses demonstrated the expression of genes encoding arachidonic acid pathway components such as COX-1, COX-2 and prostaglandin synthases in a subset of mouse taste bud cells. Double-staining immunohistochemistry revealed that COX-1 and cytosolic prostaglandin E synthase (cPGES) were co-expressed with taste receptor type-1 member-3 (T1R3), a sweet/umami receptor component, or gustducin, a bitter/sweet/umami-related G protein, in a subset of taste bud cells. Long-term administration of diclofenac reduced the expression of genes encoding COX-1, gustducin and cPGES in mouse taste buds and suppressed both the behavioral and taste nerve responses to sweet and umami taste stimuli but not to other tastants. Furthermore, diclofenac also suppressed the responses of both mouse and human sweet taste receptors (T1R2/T1R3, expressed in HEK293 cells) to sweet taste stimuli. These results suggest that diclofenac may suppress the activation of sweet and umami taste cells acutely via a direct action on T1R2/T1R3 and chronically via inhibition of the COX/prostaglandin synthase pathway inducing down-regulated expression of sweet/umami responsive components. This dual inhibition mechanism may underlie diclofenac-induced taste alterations in humans.

7.
Sci Rep ; 12(1): 21246, 2022 12 08.
Article in English | MEDLINE | ID: mdl-36481783

ABSTRACT

Little is known about the molecular mechanisms underlying drug-induced taste disorders, which can cause malnutrition and reduce quality of life. One of taste disorders is known adverse effects of bisphosphonates, which are administered as anti-osteoporotic drugs. Therefore, the present study evaluated the effects of risedronate (a bisphosphonate) on taste bud cells. Expression analyses revealed that farnesyl diphosphate synthase (FDPS, a key enzyme in the mevalonate pathway) was present in a subset of mouse taste bud and tongue epithelial cells, especially type III sour-sensitive taste cells. Other mevalonate pathway-associated molecules were also detected in mouse taste buds. Behavioral analyses revealed that mice administered risedronate exhibited a significantly enhanced aversion to HCl but not for other basic taste solutions, whereas the taste nerve responses were not affected by risedronate. Additionally, the taste buds of mice administered risedronate exhibited significantly lower mRNA expression of desmoglein-2, an integral component of desmosomes. Taken together, these findings suggest that risedronate may interact directly with FDPS to inhibit the mevalonate pathway in taste bud and tongue epithelial cells, thereby affecting the expression of desmoglein-2 related with epithelial barrier function, which may lead to alterations in behavioral responses to HCl via somatosensory nerves.


Subject(s)
Diphosphonates , Epithelial Cells , Geranyltranstransferase , Animals , Mice , Diphosphonates/pharmacology , Epithelial Cells/enzymology , Geranyltranstransferase/genetics , Quality of Life , Taste Disorders , Taste Buds/cytology , Tongue/cytology , Risedronic Acid/pharmacology
8.
Sci Rep ; 12(1): 17762, 2022 10 22.
Article in English | MEDLINE | ID: mdl-36273034

ABSTRACT

In vertebrates, the extracellular calcium-sensing receptor (CaSR) plays a key role in calcium homeostasis by sensing slight changes in extracellular Ca2+. CaSR is also expressed in mammals including rodent taste cells and is involved in sensing kokumi, a rich, savory quality that enhances the intensities of salty, sweet, and umami tastes. In this study, we focused on chicken CaSR (cCaSR) since calcium is an essential nutrient that is necessary for making eggshell and for the extremely rapid initial growth of bones. First we confirmed that cCaSR is expressed in taste cells. Next we cloned the cCaSR gene from kidney and transiently transfected human embryonic kidney 293 T (HEK293T) cells with the recombinant cCaSR, or empty vector and looked for the agonists and allosteric modulators (including kokumi substances) of cCaSR by Ca2+ imaging. We found that cCaSR was activated by extracellular Ca2+ and Mg2+ in a dose dependent manner. Several L-amino acids and kokumi substances such as glutathione enhanced the response of cCaSR. In addition, NPS2143 as a negative allosteric modulator of human CaSR negatively modulated the response of cCaSR. These results suggest that cCaSR can sense extracellular Ca2+ and Mg2+ as well as positive and negative allosteric modulators. Taken together, the results imply that CaSR might be a multifunctional receptor for calcium, amino acids, and kokumi substances in chicken. The present finding that functional CaSR is expressed in the chicken oral tissues will allow us to further elucidate the physiological role of CaSR in the chickens' taste sense, and to create new feeds that will contribute to the poultry industry.


Subject(s)
Chickens , Receptors, Calcium-Sensing , Animals , Humans , Receptors, Calcium-Sensing/metabolism , Chickens/metabolism , Calcium/metabolism , HEK293 Cells , Glutathione , Amino Acids , Mammals/metabolism
9.
Biochem Biophys Res Commun ; 632: 40-47, 2022 12 03.
Article in English | MEDLINE | ID: mdl-36198202

ABSTRACT

Autophagy is a non-selective action in which cells degrade parts of themselves, reusing degraded cellular components. Among autophagy-related gene (ATG) family members, ATG4 proteins play crucial roles in the microtubule-associated protein 1 light chain 3 (LC3) phosphatidylethanolamine (PE) system which is essential for autophagosome maturation. Although autophagy has been shown to be involved in osteoclastic bone resorption, the role of ATG4/LC3 in bone resorption remains unclear. When mouse bone marrow cells were treated with various concentrations of NSC185058 (NSC), a specific inhibitor of ATG4B, 1 h prior to treatment with receptor activator of NF-κB ligand (RANKL) in the presence of macrophage colony stimulating factor (M-CSF), NSC inhibited osteoclastogenesis in a dose-dependent manner. Addition of NSC in the late stages of osteoclast differentiation suppressed multinucleation and reduced the expression of markers for mature osteoclasts such as Dc-stamp, Mmp9, and Ctsk. NSC also suppressed actin ring formation and pit formation in mature osteoclasts. When a periodontitis model involving eight-week-old male mice in which the right maxillary second molar had been ligated with silk thread was injected with or without NSC, alveolar bone resorption was suppressed by a decrease in the number of osteoclasts in the NSC-treated group. These results suggest that LC3 is important for the maturation of osteoclasts and that LC3 inhibition is a new therapeutic strategy for periodontal disease.


Subject(s)
Cell Differentiation , Osteoclasts , Animals , Male , Mice , Actins/metabolism , Alveolar Bone Loss , Ligands , Macrophage Colony-Stimulating Factor/pharmacology , Macrophage Colony-Stimulating Factor/metabolism , Matrix Metalloproteinase 9/metabolism , Microtubule-Associated Proteins/antagonists & inhibitors , Microtubule-Associated Proteins/metabolism , Osteoclasts/metabolism , Phosphatidylethanolamines/metabolism , Receptor Activator of Nuclear Factor-kappa B/metabolism , Silk , Bone Resorption/genetics , Bone Resorption/metabolism , Cell Differentiation/genetics , Autophagy-Related Proteins/antagonists & inhibitors , Autophagy-Related Proteins/metabolism , Cysteine Endopeptidases/metabolism
10.
J Poult Sci ; 59(3): 282-285, 2022 Jul 25.
Article in English | MEDLINE | ID: mdl-35974876

ABSTRACT

It has been reported that the supplementation of chicken diet with polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA), eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA) affects the qualities of eggs and meat. Previous studies have shown that a functional fatty acid taste receptor, G protein-coupled receptor 120 (GPR120), is broadly expressed in chicken oral and gastrointestinal tissues, and chickens have a gustatory perception of oleic acid, which is a chicken GPR120 agonist. The aim of this study was to elucidate the role of chicken GPR120 in response to PUFAs in chicken diets. Ca2+ imaging analyses revealed that chicken GPR120 was activated by AA, EPA, and DHA in a concentration-dependent manner. These results suggest that chickens can detect PUFAs via GPR120 in the oral and gastrointestinal tissues, implying that chickens have a gustatory perception of PUFAs.

11.
Poult Sci ; 101(7): 101928, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35679679

ABSTRACT

Elucidating the taste sensing systems in chickens will enhance our understanding of poultry nutrition and improve the feeding strategies used in poultry farming. It is known that chickens lack the sweet taste receptor subunit, taste receptor type 1 member 2 (T1R2), in their genome. Thus, the present study investigated T1R2-independent sweet-sensing pathways in chickens. RT-PCR analysis revealed that glucose transporters known to play an important role in T1R2-independent sweet sensing in mammals-namely sodium-glucose cotransporter 1 (SGLT1) and ATP-gated K+ channel subunits-are expressed in the palate, the main taste organ in chickens. In behavioral tests, chickens slightly preferred glucose, galactose, sucrose, maltose, lactose, and stevioside, while high doses of sucrose and fructose were rejected. Chickens did not show any preference for noncaloric sweeteners or sugar alcohol, such as acesulfame K, aspartame, saccharin, sucralose, or sorbitol. The preference for galactose was inhibited by an inhibitor of SGLT1 in a dose-dependent manner. In addition, we found that glucagon-like peptide 1 (GLP-1) and mRNA of the GLP-1 receptor, which are involved specifically in sweet transmission in mice, are also present in the oral tissues of chickens. The present results imply that chickens can sense various sweet compounds via T1R2-independent pathways in oral tissues.


Subject(s)
Chickens , Taste , Animals , Chickens/metabolism , Galactose , Glucose/metabolism , Mammals/metabolism , Mice , Receptors, G-Protein-Coupled/genetics , Sucrose , Taste/physiology
12.
Biochem Biophys Res Commun ; 557: 206-212, 2021 06 11.
Article in English | MEDLINE | ID: mdl-33872990

ABSTRACT

Taste buds are complex sensory organs embedded in the epithelium of fungiform papillae (FP) and circumvallate papillae (CV). The sweet, bitter, and umami tastes are sensed by type II taste cells that express taste receptors (Tas1rs and Tas2rs) coupled with the taste G-protein α-gustducin. Recent studies revealed that the taste response profiles of α-gustducin-expressing cells are different between FP and CV, but which genes could generate such distinctive cell characteristics are still largely unknown. We performed a comprehensive transcriptome analysis on α-gustducin-expressing cells in mouse FP and CV by single-cell RNA sequencing combined with fluorescence-activated cell sorting. Transcriptome profiles of the α-gustducin-expressing cells showed various expression patterns of taste receptors. Our clustering analysis defined the specific cell populations derived from FP or CV based on their distinct gene expression. Immunohistochemistry confirmed the specific expression of galectin-3, encoded by Lgals3, which was recognized as a differentially expressed gene in the transcriptome analysis. Our work provides fundamental knowledge toward understanding the genetic heterogeneity of type II cells, potentially revealing differential characterization of FP and CV taste bud cells.


Subject(s)
Galectin 3/metabolism , Gene Expression Regulation/genetics , Taste Buds/metabolism , Tongue/metabolism , Transducin/metabolism , Animals , Cell Differentiation/genetics , Female , Galectin 3/genetics , Gene Expression Profiling , Gene Ontology , Immunohistochemistry , Male , Mice , Mice, Inbred C57BL , RNA-Seq , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Single-Cell Analysis , Taste Perception/genetics , Transducin/genetics
13.
Poult Sci ; 100(1): 372-376, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33357702

ABSTRACT

A functional fatty acid taste receptor, GPR120, is present in chicken oral tissues, and chickens show a preference for lipid in feed. However, it remains unclear whether chickens can detect fatty acids. To address this issue, we adopted 2 behavioral paradigms: a one-bowl drinking test to evaluate the preference for oleic acid solution and a conditioned taste aversion test to investigate the role of gustation in chickens' ability to detect oleic acid. In the one-bowl drinking test, chickens did not show any preference for solution containing 0.001, 0.01, 0.03, 0.1, or 30 mmol/L oleic acid although 30 mmol/L oleic acid was enough to fully activate GPR120, confirmed by Ca2+ imaging. On the other hand, chickens conditioned to avoid 30 mmol/L oleic acid solution also learned to avoid the solution. These results suggested that chickens have a gustatory perception of oleic acid solution but do not have a preference for it. The present results support the idea that chickens prefer lipid in feed, not only by a postingestive effect but also by sensing the taste of fatty acid.


Subject(s)
Avoidance Learning , Chickens , Feeding Behavior , Taste , Animals , Avoidance Learning/drug effects , Feeding Behavior/drug effects , Female , Oleic Acid/pharmacology
14.
Int J Mol Sci ; 21(23)2020 Nov 25.
Article in English | MEDLINE | ID: mdl-33255773

ABSTRACT

Taste disorders are common adverse effects of cancer chemotherapy that can reduce quality of life and impair nutritional status. However, the molecular mechanisms underlying chemotherapy-induced taste disorders remain largely unknown. Furthermore, there are no effective preventive measures for chemotherapy-induced taste disorders. We investigated the effects of a combination of three anticancer drugs (TPF: docetaxel, cisplatin and 5-fluorouracil) on the structure and function of mouse taste tissues and examined whether the drinking of ice-cold water after TPF administration would attenuate these effects. TPF administration significantly increased the number of cells expressing apoptotic and proliferative markers. Furthermore, TPF administration significantly reduced the number of cells expressing taste cell markers and the magnitudes of the responses of taste nerves to tastants. The above results suggest that anticancer drug-induced taste dysfunction may be due to a reduction in the number of taste cells expressing taste-related molecules. The suppressive effects of TPF on taste cell marker expression and taste perception were reduced by the drinking of ice-cold water. We speculate that oral cryotherapy with an ice cube might be useful for prophylaxis against anticancer drug-induced taste disorders in humans.


Subject(s)
Head and Neck Neoplasms/diet therapy , Ice , Taste Disorders/diet therapy , Water/pharmacology , Animals , Cell Proliferation/drug effects , Cisplatin/adverse effects , Disease Models, Animal , Docetaxel/adverse effects , Fluorouracil/adverse effects , Head and Neck Neoplasms/complications , Head and Neck Neoplasms/pathology , Humans , Mice , Taste Disorders/chemically induced , Taste Disorders/pathology , Taxoids/adverse effects , Water/chemistry
15.
Biochem Biophys Res Commun ; 515(2): 386-393, 2019 07 23.
Article in English | MEDLINE | ID: mdl-31155288

ABSTRACT

Chickens, one of the most important industrial animals, are a biological animal model. Here we focused on the transient receptor potential vanilloid 1 (TRPV1) to understand the pain system for acidic stimuli in chickens compared with mice. By using a whole-cell patch clamp system, we confirmed that acidic stimuli activate both chicken TRPV1 (cTRPV1) and mouse TRPV1 (mTRPV1), but the peak current of cTRPV1 is lower than that of mTRPV1, and it is difficult to desensitize cTRPV1 with an acidic stimulus compared to mTRPV1. Since the C-terminal of the calmodulin (CaM) binding site in TRPV1 was reported as one of the important structures for TRPV1 desensitization, we made chimeric cTRPV1 in which the CaM binding site of chicken is changed to that of mouse (cTRPV1-mCaM). We also compared the acidic responses of native chicken dorsal root ganglion (DRG) cells with that of mouse DRG cells. The TRPV1-mCaM results showed that the desensitization of mutant cTRPV1 was similar to that of mTRPV1, and that the basal activities of mutant cTRPV1 were significantly higher than those of cTRPV1. It was also difficult to desensitize the chicken DRG cells with an acidic stimulus, unlike the mouse DRG cells. These results suggest that there are differences in the pain transduction systems for acidic stimuli between chickens and mice that are caused by the dysfunction of the C-terminal CaM biding site of cTRPV1. These results imply that chickens repeatedly feel weak pain from an acidic stimulus, without desensitization.


Subject(s)
Avian Proteins/metabolism , TRPV Cation Channels/metabolism , Amino Acid Sequence , Animals , Avian Proteins/chemistry , Avian Proteins/genetics , Binding Sites/genetics , Calmodulin/metabolism , Capsaicin/pharmacology , Cells, Cultured , Chickens , Ganglia, Spinal/cytology , Ganglia, Spinal/drug effects , Ganglia, Spinal/metabolism , HEK293 Cells , Humans , Hydrogen-Ion Concentration , Mice , Mice, Inbred C57BL , Mutant Chimeric Proteins/chemistry , Mutant Chimeric Proteins/genetics , Mutant Chimeric Proteins/metabolism , Patch-Clamp Techniques , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Species Specificity , TRPV Cation Channels/chemistry , TRPV Cation Channels/genetics
16.
Biomed Res ; 39(6): 279-286, 2018.
Article in English | MEDLINE | ID: mdl-30531157

ABSTRACT

Transient receptor potential vanilloid 1 (TRPV1) is a nociceptive cation channel that is activated by heat, protons and chemical ligands such as capsaicin. We investigated the roles of the capsaicin receptor, TRPV1, in controlling the energy metabolism of the whole body. It has been reported that the activation of TRPV1 by its agonists enhances energy metabolism. In this study, we used a respiratory gas analysis system to examine whether the inhibition of TRPV1 changes energy metabolism in mice. In addition, we examined the contributions of different modes of TRPV1 activation (heat, protons and capsaicin) to determine the influence of 3 different TRPV1 antagonists on energy metabolism. Here, we showed that intragastric administration of AMG517, a nonselective antagonist of TRPV1 (for heat, protons and capsaicin), enhanced energy metabolism as much as did intraperitoneal administration. On the other hand, intraperitoneal administration of AMG9810, a nonselective antagonist like AMG517, enhanced energy expenditure more than intragastric administration. However, the administration of JYL1421, a TRPV1 antagonist that very strongly inhibits TRPV1 activated by capsaicin, did not change energy metabolism. Taken together, these results suggest that the type of TRPV1 antagonists and the routes of its administration have different effects on energy metabolism in a normal body. Surprisingly, co-administration of JYL1421 and capsaicin significantly enhanced the energy metabolism more than administration of capsaicin alone. These results support the possibility that an unconventional mechanism is responsible for the increase in energy metabolism that occurs via TRPV1 inhibition.


Subject(s)
Energy Metabolism , TRPV Cation Channels/antagonists & inhibitors , Animals , Benzothiazoles/pharmacology , Capsaicin/pharmacology , Mice , Mice, Inbred C57BL , Oxygen Consumption/drug effects , Pyrimidines/pharmacology , Sulfonamides/pharmacology , Thiourea/analogs & derivatives , Thiourea/pharmacology
17.
Physiol Behav ; 191: 29-36, 2018 07 01.
Article in English | MEDLINE | ID: mdl-29588172

ABSTRACT

Umami taste is one of the five basic tastes (sweet, umami, bitter, sour, and salty), and is elicited by l-glutamate salts and 5'-ribonucleotides. In chickens, the elucidation of the umami taste sense is an important step in the production of new feedstuff for the animal industry. Although previous studies found that chickens show a preference for umami compounds in long-term behavioral tests, there are limitations to our understanding of the role of the umami taste sense in chicken oral tissues because the long-term tests partly reflected post-ingestive effects. Here, we performed a short-term test and observed agonists of chicken umami taste receptor, l-alanine and l-serine, affected the solution intakes of chickens. Using this method, we found that chickens could respond to umami solutions containing monosodium l-glutamate (MSG) + inosine 5'-monophosphate (IMP) within 5 min. We also demonstrated that chickens were successfully conditioned to avoid umami solution by the conditioned taste aversion test. It is noted that conditioning to umami solution was generalized to salty and sweet solutions. Thus, chickens may perceive umami taste as a salty- and sweet-like taste. In addition, we found that umami taste receptor candidates were differentially expressed in different regions of the chicken oral tissues. Taken together, the present results strongly suggest that chickens have a sense of umami taste and have umami taste receptors in their oral tissue.


Subject(s)
Avoidance Learning/physiology , Gene Expression Regulation/drug effects , Inosine Monophosphate/pharmacology , Receptors, G-Protein-Coupled/metabolism , Taste Perception/physiology , Taste/physiology , Analysis of Variance , Animals , Animals, Newborn , Avoidance Learning/drug effects , Chickens , Dose-Response Relationship, Drug , Glutamic Acid/pharmacology , Piperidines/pharmacology , RNA, Messenger/metabolism , Receptors, G-Protein-Coupled/genetics , Taste/drug effects , Taste Perception/drug effects , Time Factors
18.
J Poult Sci ; 55(3): 204-209, 2018.
Article in English | MEDLINE | ID: mdl-32055176

ABSTRACT

Bitterness is one of the five basic tastes, and sensitivity to bitterness is important in that it enables animals to avoid harmful and toxic substances. In humans, taste sensitivity decreases with age, although the extent of loss varies depending on the taste quality. In chickens (Gallus gallus domesticus), baby chicks have been found to be more sensitive to salt and sour taste qualities than adults. In this study, therefore, we investigated the growth-associated changes in bitter taste sensitivity in chicks. We examined the behavioral perceptions toward the bitter compounds chloramphenicol and andrographolide in chicks at three different growth stages. Then, we measured the relative expression of the functional bitter taste receptors in the chick palate. In behavioral drinking tests, the 0-1-week-old chicks consumed a significantly lower amount of bitter solutions than water, whereas the 8-9-week-old chicks showed lower avoidance of the bitter solutions than the 0-1-week-old and 4-5-week-old chicks. Real-time PCR assay showed that the 0-1-week-old chicks had significantly higher expression of one of the functional bitter taste receptors in the palate than that in the older chicks. These results suggest that baby chicks are more sensitive to bitterness than older chicks. These findings may be useful in the production of new feedstuff for chicks according to their growth stages.

19.
Anim Sci J ; 89(2): 441-447, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29178505

ABSTRACT

The elucidation of the mechanisms underlying the taste sense of chickens will contribute to improvements in poultry feeding, because the molecular mechanism of chickens' taste sense defines the feeding behavior of chickens. Here we focused on the gene expressions in two different oral tissues of chickens - the palate, which contains many taste buds, and the tongue tip, which contains few taste buds. Using the quantitative real-time polymerase chain reaction method, we found that the molecular markers for taste buds of chickens, that is α-gustducin and vimentin, were expressed significantly highly in the palate compared to the tongue tip. Our analyses also revealed that transient receptor potential subfamily M member 5 (TRPM5), a cation channel involved in taste transduction in mammals, was also highly expressed in the palate compared to the tongue tip. Our findings demonstrated that the expression patterns of these genes were significantly correlated. We showed that the aversion to bitter solution was alleviated by a TRPM5 inhibitor in behavior of chickens. Taken together, our findings enabled us to develop a simple method for screening taste-related genes in chickens. The use of this method demonstrated that TRPM5 was involved in chickens' taste transduction, and that a TRPM5 inhibitor can alleviate chickens' bitter taste perception of feed ingredients.


Subject(s)
Chickens/physiology , Gene Expression , Palate/metabolism , TRPM Cation Channels/metabolism , TRPM Cation Channels/physiology , Taste/genetics , Tongue/metabolism , Animals , Feeding Behavior , Real-Time Polymerase Chain Reaction , Taste/physiology
20.
Biochem Biophys Res Commun ; 495(1): 131-135, 2018 01 01.
Article in English | MEDLINE | ID: mdl-29080746

ABSTRACT

It has been reported that a functional fat-taste receptor, GPR120, is present in chicken oral tissues, and that chickens can detect fat taste in a behavioral test. However, although triglycerides need to be digested to free fatty acids to be recognized by fat-taste receptors such as GPR120, it remains unknown whether lipase activities exist in chicken oral tissues. To examine this question, we first cloned another fat-taste receptor candidate gene, CD36, from the chicken palate. Then, using RT-PCR, we determined that GPR120 and CD36 were broadly expressed in chicken oral and gastrointestinal tissues. Also by RT-PCR, we confirmed that several lipase genes were expressed in both oral and gastrointestinal tissues. Finally, we analyzed the lipase activities of oral tissues by using a fluorogenic triglyceride analog as a lipase substrate. We found there are functional lipases in oral tissues as well as in the stomach and pancreas. These results suggested that chickens have a basic fat-taste reception system that incorporates a triglycerides/oral-lipases/free fatty acids/GPR120 axis and CD36 axis.


Subject(s)
CD36 Antigens/metabolism , Chickens/physiology , Dietary Fats/metabolism , Lipase/metabolism , Receptors, G-Protein-Coupled/metabolism , Taste , Amino Acid Sequence , Animals , Base Sequence , CD36 Antigens/analysis , CD36 Antigens/genetics , Chickens/genetics , Cloning, Molecular , Fatty Acids, Nonesterified/metabolism , Gene Expression , Lipase/analysis , Lipase/genetics , Palate/metabolism , Receptors, G-Protein-Coupled/analysis , Receptors, G-Protein-Coupled/genetics , Taste Buds/physiology , Taste Perception , Triglycerides/metabolism
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