Chemical Senses最新文献

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.

In behavioral experiments, rats perceive sodium carbonate (Na2CO3) as super salty. In fact, when the dissociated Na+ ions are accounted for, rats perceive Na2CO3 as 5× saltier than equinormal concentrations of NaCl. The chorda tympani nerve (CT) responds to salts through at least two receptor mechanisms and is a model system for understanding how salt taste is transmitted to the brain. Here, we recorded CT nerve activity to a broad range of NaCl (3-300 mM) and Na2CO3 (3-300 mN) to investigate why Na2CO3 tastes so salty to rats. Benzamil, a specific epithelial sodium channel (ENaC) antagonist, was used to determine the relative contribution of apical ENaCs in Na2CO3 transduction. The benzamil-insensitive component of CT nerve responses was enhanced by increasing the adapted tongue temperature from 23°C to 30°C. Na2CO3 solutions are alkaline, so we compared neural responses (with and without benzamil) to 100 mM NaCl alone (6.2 pH) and at a pH (11.2 pH) that matched 100 mN Na2CO3. As expected, NaCl responses increased progressively with increasing concentration and temperature. Responses to 3 mN Na2CO3 were greater than 3 mM NaCl with and without benzamil, but the shape of the first log-fold range of was relatively flat. Adjusting the pH of NaCl to 11.2 abolished the thermal enhancement of 100 mN NaCl through the benzamil-insensitive pathway. Rinsing Na2CO3 off the tongue resulted in robust aftertaste that was concentration dependent, thermally sensitive, and benzamil-insensitive. Responses to alkaline NaCl did not recapitulate Na2CO3 responses or aftertaste, suggesting multiple transduction mechanisms for the cations (2Na+) and anion (CO3-2).

High concentrations of dietary salt are harmful to health. Like most animals, Drosophila melanogaster are attracted to foods that have low concentrations of salt, but show strong taste avoidance of high salt foods. Salt in known on multiple classes of taste neurons, activating Gr64f sweet-sensing neurons that drive food acceptance and 2 others (Gr66a bitter and Ppk23 high salt) that drive food rejection. Here we find that NaCl elicits a bimodal dose-dependent response in Gr64f taste neurons, which show high activity with low salt and depressed activity with high salt. High salt also inhibits the sugar response of Gr64f neurons, and this action is independent of the neuron's taste response to salt. Consistent with the electrophysiological analysis, feeding suppression in the presence of salt correlates with inhibition of Gr64f neuron activity, and remains if high salt taste neurons are genetically silenced. Other salts such as Na2SO4, KCl, MgSO4, CaCl2, and FeCl3 act on sugar response and feeding behavior in the same way. A comparison of the effects of various salts suggests that inhibition is dictated by the cationic moiety rather than the anionic component of the salt. Notably, high salt-dependent inhibition is not observed in Gr66a neurons-response to a canonical bitter tastant, denatonium, is not altered by high salt. Overall, this study characterizes a mechanism in appetitive Gr64f neurons that can deter ingestion of potentially harmful salts.

The presence of a perceptual bias due to anxiety is well demonstrated in cognitive and sensory task for the visual and auditory modality. Event-related potentials, by their specific measurement of neural processes, have strongly contributed to this evidence. There is still no consensus as to whether such a bias exists in the chemical senses; chemosensory event-related potentials (CSERPs) are an excellent tool to clarify the heterogeneous results, especially since the Late Positive Component (LPC) may be an indicator of emotional involvement after chemosensory stimulation. This research examined the association between state and trait anxiety and the amplitude and latency of pure olfactory and mixed olfactory-trigeminal LPC. In this study, 20 healthy participants (11 women) with a mean age of 24.6 years (SD = 2.6) completed a validated questionnaire to measure anxiety (STAI), and CSERP was recorded during 40 pure olfactory stimulations (phenyl ethanol) and 40 mixed olfactory-trigeminal stimulations (eucalyptol). LPC latency and amplitude were measured at Cz (electrode located at midline central) for each participant. We observed a significant negative correlation between LPC latencies and the state anxiety scores for the mixed olfactory-trigeminal condition (r(18) = -0.513; P = 0.021), but not for the pure olfactory condition. We did not observe any effect on LPC amplitudes. This study suggests that a higher level of state anxiety is related to a more rapid perceptual electrophysiological response for mixed olfactory-trigeminal stimuli but not for pure odors.

While accumulating evidence implied the involvement of retro-nasal sensation in the consumption of nonvolatile taste compounds, it is still unclear whether it was caused by the taste compounds themselves, and if so, how can they migrate from the oral to nasal cavity. At first, we proposed aerosol particles as an alternative oral-nasal mass transfer mechanism. The high-speed camera approved that aerosol particles could be generated by the typical oral and pharynx actions during food oral processing; while the narrow-band imaging of nasal cleft and mass spectrometry of nostril-exhaled air approved the migration of aerosol within the oral-nasal route. Then, the "smelling" of taste compounds within the aerosol particles was testified. The four-alternative forced choices (4AFC) approved that the potential volatile residues or contaminants within the headspace air of pure taste solution cannot arouse significant smell, while the taste compounds embedded in the in vitro prepared aerosol particles can be "smelled" via the ortho route. The "smell" of sucrose is very different from its taste and the "smell" of quinine, implying its actual olfaction. The sweetness intensity of sucrose solution was also reduced when the volunteers' noses were clipped, indicating the involvement of retro-nasal sensation during its drinking. At last, the efficiency of aerosol as a mechanism of oral-nasal mass transfer was demonstrated to be comparable with the volatile molecules under the experimental condition, giving it the potential to be a substantial and unique source of retro-nasal sensation during food oral processing.

Lopinavir and ritonavir (LPV/r) are the primary anti-human immunodeficiency virus (HIV) drugs recommended by the World Health Organization for treating children aged 3 years and above who are infected with the HIV. These drugs are typically available in liquid formulations to aid in dosing for children who cannot swallow tablets. However, the strong bitter taste associated with these medications can be a significant obstacle to adherence, particularly in young children, and can jeopardize the effectiveness of the treatment. Studies have shown that poor palatability can affect the survival rate of HIV-infected children. Therefore, developing more child-friendly protease inhibitor formulations, particularly those with improved taste, is critical for children with HIV. The molecular mechanism by which lopinavir and ritonavir activate bitter taste receptors, TAS2Rs, is not yet clear. In this study, we utilized a calcium mobilization assay to characterize the activation of bitter taste receptors by lopinavir and ritonavir. We discovered that lopinavir activates TAS2R1 and TAS2R13, while ritonavir activates TAS2R1, TAS2R8, TAS2R13, and TAS2R14. The development of bitter taste blockers that target these receptors with a safe profile would be highly desirable in eliminating the unpleasant bitter taste of these anti-HIV drugs.

The underlying mechanisms of taste interactions in humans are not well understood, and three mechanisms have been proposed, namely a chemical interaction, a peripheral physiological, and a central mechanism. In the present study, it was investigated which of these mechanisms causes the suppression of sweetness by citric acid. This was investigated using a split-tongue gustometer that can stimulate the two sides of the tongue with different stimuli simultaneously, enabling a comparison of sucrose and citric acid presented either separately on each side of the tongue simultaneously or in a mixture on one side. Two studies were conducted using low (Study 1; n = 50) and high (Study 2: n = 59) concentrations of sucrose (2.5% (w/w) and 10% (w/w), respectively), and citric acid (0.14% (w/w) and 0.18% (w/w), respectively). In neither of the studies was there a significant difference in sweetness intensity ratings between the two conditions where sucrose and citric acid were presented either separately or in a mixture form. However, both showed significantly lower sweetness ratings than without citric acid indicating suppression of the sweetness of sucrose from citric acid. This provides strong evidence for a central mechanism for the suppression of the sweetness of sucrose by citric acid. This mechanism seems to be equal in high and low concentrations of both sucrose and citric acid.

We have previously shown that l-glucose, the non-caloric enantiomer of d-glucose, activates the human sweet taste receptor T1R2/T1R3 transiently expressed in HEK293T cells. Here, we show that d- and l-glucose can also activate T1R2 and T1R3 expressed without the counterpart monomer. Serine mutation to alanine in residue 147 in the binding site of T1R3 VFT domain, completely abolishes T1R3S147A activation by either l- or d-glucose, while T1R2/T1R3S147A responds in the same way as T1R2 expressed without its counterpart. We further show that the original T1R2 reference sequence (NM_152232.1) is less sensitive by almost an order of magnitude than the reference sequence at the time this study was performed (NM_152232.4). We find that out of the four differing positions, it is the R317G in the VFT domain of T1R2, that is responsible for this effect in vitro. It is significant for both practical assay sensitivity and because glycine is found in this position in ~20% of the world population. While the effects of the mutations and the partial transfections were similar for d and l enantiomers, their dose-response curves remained distinct, with l-glucose reaching an early plateau.

Wolfram syndrome is a rare disease characterized by diabetes, neurodegeneration, loss of vision, and audition. We recently found, in a young sample of participants (mean age 15 years), that Wolfram syndrome was associated with impairment in smell identification with normal smell sensitivity and whole-mouth taste function. However, these senses were assessed separately, and it is unknown whether smell-taste interactions are altered in Wolfram syndrome, which was the focus of this study. Participants with Wolfram syndrome (n = 36; 18.2 ± 6.8 years) and sex-age-equivalent healthy controls (n = 34) were assessed with a battery of sensory tests. Using sip-and-spit methods, participants tasted solutions containing gustatory and olfactory stimuli (sucrose with strawberry extract, citric acid with lemon extract, sodium chloride in vegetable broth, and coffee) with and without nose clips, and rated perceived taste and retronasal smell intensities using the generalized Labeled Magnitude Scale. Participants also completed n-butanol detection thresholds and the University of Pennsylvania Smell Identification Test (UPSIT). Retronasal smell increased taste intensity of sucrose, sodium chloride, and coffee solutions similarly in both groups (P values <0.03). Compared with the control group, participants in the Wolfram group had lower UPSIT scores and reduced smell sensitivity, retronasal intensity, and saltiness (P values <0.03), but rated other taste intensities similarly when wearing the nose clip. Despite impairments in orthonasal smell identification, odor-induced taste enhancement was preserved in participants with Wolfram syndrome who still had some peripheral olfactory function. This finding suggests that odor-induced taste enhancement may be preserved in the presence of reduced olfactory intensity.