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Receptors for bitter, sweet and umami taste couple to inhibitory G protein signaling pathways.

Taste receptors are thought to couple to the G protein Galpha-gustducin to initiate signal transduction cascades leading to taste perception. To further characterize the G protein-coupling selectivity of these receptors, we expressed them in HEK293 cells and monitored the modulation of different signaling pathways upon stimulation. We found that the bitter compound cycloheximide induces phosphorylation of extracellular signal-regulated kinases1 and 2 (ERK 1/2) and inhibits cAMP accumulation in HEK293 cells expressing the mouse bitter T2R(5) receptor. These effects are totally abolished upon treatment with pertussis toxin. On the other hand, sweeteners and monosodium glutamate induce phosphorylation of ERK1/2 and inhibit cAMP accumulation in HEK293 cells expressing the human sweet T1R(2)/T1R(3) receptor and the human umami T1R(1)/T1R(3) receptor, respectively. The effects of these taste modalities are also prevented by treatment with pertussis toxin. Collectively, our results show that taste receptors can functionally couple to Galpha(i/o) proteins to transmit intracellular signals.

Adenylyl Cyclase Inhibitors↗

Naloxone effects on sucrose-motivated behavior.

The opioid system plays an important role in feeding. In general, opioid agonists typically increase feeding and opioid antagonists decrease feeding in non-food restricted animals. In food restricted animals the effects of these drugs are substantially reduced. Opioid antagonists have shown a marked effectiveness at reducing consumption of sweet foods. Explanations for this robust effect have typically focused on drug induced changes in taste, taste perception, or palatability. The current study relates the effects of the opioid antagonist naloxone on motivation to obtain different sucrose concentrations to the drug's effects on unrestricted sucrose solution consumption. Changes in motivation to respond were assessed under a progressive ratio reinforcement schedule (PR) which required increased response cost for each successive unit of sucrose solution. Motivation, as measured by the PR, increased as sucrose concentration increased and naloxone produced a dose-dependent decrease in motivation to respond for a given sucrose concentration. Thus, the effectiveness of naloxone was indirectly related to strength of the sucrose concentration. Under unrestricted access to sucrose solutions, naloxone reduced consumption greatest under the higher concentrations. The data suggest at least part of naloxone's effects on sweet tasting food may be mediated through endogenous opioid reward systems that are reflected in measures of motivation.

Animals↗

Multicenter, double-blind, multiple-dose, parallel-groups efficacy and safety trial of azelastine, chlorpheniramine, and placebo in the treatment of spring allergic rhinitis.

Azelastine, a novel antiallergic medication, was compared with chlorpheniramine maleate and placebo for efficacy and safety in the treatment of spring allergic rhinitis in a multicenter, double-blind, multiple-dose, parallel-groups study. One hundred fifty-five subjects participated. Subjects ranged in age from 18 to 60 years of age and had at least a 2-year history of spring allergic rhinitis, confirmed by positive skin test to spring aeroallergens. Medications were given four times daily; the azelastine groups received 0.5, 1.0, or 2.0 mg in the morning and evening with placebo in the early and late afternoon; the chlorpheniramine group received 4.0 mg four times daily. Daily subject symptom cards were completed during a screening period to assess pretreatment symptoms and during a 4-week treatment period while subjects received study medications. Individual symptoms, total symptoms, and major symptoms were compared to determine efficacy of medication. Elicited, volunteered, and observed adverse experiences were recorded for each subject and compared among groups. Vital signs, body weights, serum chemistry values, complete blood cell counts, urine studies, and electrocardiograms were obtained for each subject and compared among groups. Symptoms relief in the group receiving the highest concentration of azelastine (2.0 mg twice daily) was statistically greater than in the placebo group during all weeks of the study. Lower doses of azelastine were statistically more effective than placebo only during portions of the first 3 weeks of the study. In contrast, although the chlorpheniramine group did have fewer symptoms than the placebo group during the study, the difference never reached statistical significance during any week of the study. There were no serious side effects in any of the treatment groups. Drowsiness and altered taste perception were increased significantly over placebo only in the high-dose azelastine group. Azelastine appears to be a safe, efficacious medication for seasonal allergic rhinitis.

Adolescent↗

Taste and smell sensations enhance the satiating effect of both a high-carbohydrate and a high-fat meal in humans.

The effects of meal sensory properties (tasty vs. bland) and nutrient composition [high-CHO (carbohydrate) vs. high-FAT] on hunger ratings, blood glucose and free fatty acids (FFA), taste perception, and subsequent food intake, were studied in human subjects. Aspartame and vanilla were used to augment meal palatability, yielding four isocaloric liquid meals: bland-FAT, tasty-FAT, bland-CHO, tasty-CHO. Normal-weight, nondieting young adults consumed each of the meals for breakfast on separate days. The main finding was that tasty versions of high-FAT and high-CHO meals were more satiating than nutritionally identical bland meals, as indicated by a greater decrease in hunger ratings following the tasty meals. Changes in blood glucose and FFA were related to meal nutrient composition, but not to meal sensory properties. High-CHO meals tended to be more satiating than high-FAT meals. Consumption of each of the meals produced a similar decrease in pleasantness ratings of food-related tastes. Intake of carbohydrates was significantly higher at a self-selected lunch 5.25 h following a tasty breakfast. These findings indicate that hunger is decreased to a greater extent by meals flavored with aspartame and vanilla relative to nutritionally identical, unflavored meals. The satiety-enhancing effect of oral stimulation was found for both high-FAT and high-CHO meals.

Adult↗

Perceptual integration of tertiary taste mixtures.

Integration psychophysics was used to explore the taste perception of mixtures of sucrose, fructose, and citric acid. Three levels of each stimulus were varied in a 3 x 3 x 3 factorial design. Subjects rated total intensity, sweetness, and acidity of the 27 mixtures on graphic rating scales. Consistent with earlier work, the perceived total intensity of the tertiary mixtures was found to be dictated by the intensity of the (subjectively) stronger component alone (i.e., either the integrated sweetness or the acidity, whichever was the more intense). In contrast, the sweetness and acidity of the mixture were susceptible to mutual suppression: Sweetness suppressed acidity, acidity suppressed sweetness. There was, however, a difference between sucrose and fructose in their interactions with citric acid, fructose being the more susceptible to suppression. This selectivity of suppression indicates that the two sweetnesses could not have been inextricably integrated. Implications for taste coding are discussed, and the findings are reconciled in terms of two separate coding mechanisms: one for taste intensity, another for taste quality.

Adult↗

Calcium: taste, intake, and appetite.

This review summarizes research on sensory and behavioral aspects of calcium homeostasis. These are fragmented fields, with essentially independent lines of research involving gustatory electrophysiology in amphibians, ethological studies in wild birds, nutritional studies in poultry, and experimental behavioral studies focused primarily on characterizing the specificity of the appetite in rats. Recently, investigators have begun to examine potential physiological mechanisms underlying calcium intake and appetite. These include changes in the taste perception of calcium, signals related to blood calcium concentrations, and actions of the primary hormones of calcium homeostasis: parathyroid hormone, calcitonin, and 1,25-dihydroxyvitamin D. Other influences on calcium intake include reproductive and adrenal hormones and learning. The possibility that a calcium appetite exists in humans is discussed. The broad range of observations documenting the existence of a behavioral limb of calcium homeostasis provides a strong foundation for future genetic and physiological analyses of this behavior.

Animals↗

[Taste sensitivity in homeotic mutants of the drosophila leg-arista-wing complex].

It is well established that taste chemoreceptors in Drosophila are located on the tarsi of the first leg pair. In order to investigate the influence of the novel homeotic arista-tarsus transformation on behavior, an analysis of taste perception in the lawc-mutants, characterized by the transformation of the arista into tarsus elements, was carried out. The data were subjected to thorough statistical treatment. It was shown that elements of an additional leg that appeared as a result of homeotic transformation of the arista were sensitive to gustatory stimuli. Analysis of the innervation of the homeotic organs by means of cobalt staining of afferent projections showed that the afferents starting from the homeotic leg reached the thoracic ganglion.

Animals↗

Morphological features of the minor salivary glands.

The minor salivary glands are important components of the oral cavity, present in most parts of the mouth, and their secretions directly bathe the tissues. Individual glands are usually in the submucosa between muscle fibres, and consist of groups of secretory endpieces made up of mucous acinar cells and serous or seromucous demilune cells. The ductal systems comprise intercalated ducts, intralobular ducts usually lacking basal striations, and excretory ducts opening directly through the mucosa Minor glands secrete highly glycosylated mucins, containing blood group determinants, and probably active in tissue lubrication and bacterial aggregation. They also secrete several antimicrobial proteins and immunoglobulins, and the lingual serous (von Ebner's) glands secrete digestive enzymes and proteins with possible taste perception functions. Minor gland morphology and function can conveniently be studied in the rat. There are substantial differences between major and minor salivary glands, as well as among the minor glands, in the nature and composition of their mucous and serous secretory products. The role of minor salivary glands in the function and defence of the oral cavity may be better understood as a result of new physiological and molecular methods applicable to samples of limited size and availability.

Animals↗

Taste and food preference changes across the course of pregnancy.

The present study investigates taste and specific food consumption changes across the course of pregnancy. These variables could potentially play a role in excess pregnancy-associated weight gains. Pregnant and postpartum women were asked to consume a series of everyday foods in the laboratory. Consumption and taste perception of each food were measured. In contrast to the self-report literature on cravings and aversions during pregnancy, which emphasizes changes in the first trimester, this study found that women in the second trimester consumed significantly more sweet food, but not salty or non-sweet/non-salty food, as compared with women at any other point in pregnancy. Subjects were restrained eaters, and so possibly refrained from daily consumption of excess sweet foods. This study suggests that psychological variables may interact with behavioral and physiological variables to control food preferences and eating in pregnancy.

Adult↗

Is taste related to anorexia in cancer patients?

Intensity and pleasantness of five suprathreshold concentrations each of citric acid, NaCl, urea, and sucrose in beverages were scaled by 62 patients with primary tumors in upper gastrointestinal or thoracic areas, 22 of whom had chemotherapy within the month before testing. Mean intensity scores directly correlated with concentration of sour, salty, bitter, and sweet stimuli and indicated no abnormalities of taste perception among patients grouped by tumor site, therapy, or appetite. In contrast, mean hedonic functions differed among individuals and groups. Patients on chemotherapy were less likely to display a distinct preference for any of the five concentrations of sucrose, particularly high levels, than those not on chemotherapy. Anorectics were more likely to prefer lower sweetness levels than nonanorectics, but sweet foods constituted a greater percentage of their daily caloric intake. Current theories for regulation of hunger and satiety were examined to elucidate the pathogenesis of anorexia in cancer patients.

Aged↗

Effect of the nucleoside analogs zidovudine, didanosine, stavudine, and lamivudine on the sense of taste.

The purpose of this study was to investigate the taste properties of nucleoside analogs, which are among the current medications used to treat human immunodeficiency virus (HIV) infection. Eighteen unmedicated HIV-positive subjects and 41 healthy control subjects participated in threshold and suprathreshold experiments. All of the nucleoside medications tested were perceived as predominantly bitter (along with other qualities such as metallic, medicinal, sour, astringent, and cooling). The nucleoside analog with the lowest detection thresholds was zidovudine; the detection threshold was 1.47 mM for HIV-infected patients and 2.15 mM for control subjects. Detection thresholds for lamivudine were 4.41 mM for HIV-infected patients and 4.36 mM for control subjects. Detection thresholds for stavudine were 6.39 mM for HIV-infected patients and 5.99 mM for control subjects. Detection thresholds for didanosine were 14.29 mM for HIV-infected patients and 24.0 mM for control subjects. The nucleoside analogs also modified the taste perception of KCl and CaCl2. There were no significant differences between HIV-infected subjects and control subjects for detection threshold values for any of the drugs. However, HIV-infected subjects rated lamivudine, zidovudine, and stavudine as significantly more bitter than did the control subjects at concentrations four times higher than their detection thresholds. This result was not due to use of medications by HIV-infected subjects because none of the subjects (neither HIV-infected nor control) were taking medications.

Adult↗

Taste of glutamate salts in young and elderly subjects: role of inosine 5'-monophosphate and ions.

Taste sensitivity to five glutamate salts (sodium glutamate, potassium glutamate, ammonium glutamate, calcium diglutamate, and magnesium diglutamate) were determined in sixteen young (mean age 25.58 years) and eighteen elderly (mean age 86.89 years) subjects. The effect of inosine 5'-monophosphate (IMP) and ions on taste perception of glutamate compounds was also investigated. The detection thresholds for glutamate salts were 5.04 times higher in elderly subjects than in young subjects; the recognition thresholds were 3.84 times higher. For young subjects, 0.1 mM IMP lowered detection and recognition thresholds for all 5 salts. A stronger concentration of IMP (1 mM) had this effect in both young and elderly groups. Elderly subjects perceived suprathreshold concentrations as less intense than young subjects. Chloride and acetate salts of sodium, potassium, and calcium reduced the detection and recognition thresholds of L-glutamic acid but had no effect sodium glutamate thresholds.

Adult↗

Fluid replacement preferences in heat-exposed workers.

This study examined fluid intake, weight changes, and palatability of water and a carbohydrate-electrolyte (ECHO) beverage in two groups of eight subjects performing 4 hours of simulated industrial work while wearing impermeable protective clothing. Subjects also rated the palatability of a flavorless orange-colored water and four commercially available orange-flavored fluid-replacement drinks. Subjects worked 30 min at 300 Kcal/hour (moderate work rate), followed by 30 min of rest for a total of 4 hours in each of three environments: 18, 23, 27 degrees C wet bulb globe temperature (WBGT). Eight subjects drank water and eight drank an ECHO beverage (Drink 1). Mean sweat production was similar between groups at each WBGT, (p > 0.05). Mean weight changes expressed as percentage of total body weight for the water-drinking group were -0.25 (+/- 0.16) kg in 18 degrees C, -0.55 (+/- 0.09) kg in 23 degrees C, and -0.93 (+/- 0.13) kg in 27 degrees C. Mean weight changes for the ECHO-drinking group were 0.49 (+/- 0.12) kg in 18 degrees C, 0.13 (+/- 0.12) kg in 23 degrees C, and -0.02 (+/- 0.14) kg in 27 degrees C. Each change was significantly different from that of the water-drinking group at the same temperatures (p < 0.05). Mean pre- to post-trial palatability rating results for all temperatures revealed differences in taste perception with strong preferences for Drinks 1 and 2 (pre to post): Drink 1, 3.8 to 3.6; Drink 2, 3.8 to 3.7; Drink 3, 3.0 to 2.7, Drink 4 (water), 3.2 to 3.0, and Drink 5, 2.1 to 1.6. Drinks 1 and 2 were rated significantly more palatable (p < 0.05) than Drink 3. All drinks had a reduced flavor appeal from 3.18 (+0.96) preratings to 2.92 (+1.01) postratings (p < 0.05). Mean voluntary consumption during work across the three temperatures was 1561.5 mL (+/- 720.1) for ECHO versus 1062.7 mL (+/- 666.4) for water (p = 0.054). The water group experienced greater weight loss than the ECHO group, suggesting a greater rate of dehydration when water was used for fluid replacement.

Adult↗

Water and electrolyte replenishment in the exercising child.

This article reviews studies, mostly from the authors' laboratory, on children's sweating rates and composition, voluntary drinking patterns during prolonged exercise in the heat, taste perception of beverages, and the importance of fluid flavor and composition in preventing voluntary dehydration. Subjects were children, exposed for 90 to 180 min to intermittent bouts of cycling (45-50% maximal O2 uptake) in a climatic chamber (mostly at 35 degrees C, 40-50% relative humidity). There were five main findings: When given unflavored water ad libitum, children dehydrated progressively and their core temperature increased faster than in adults. When offered drinks with various flavors, children preferred grape to other flavors. When given grape-flavored water during intermittent exercise in the heat, children voluntarily drank 44.5% more than with unflavored water. When given grape-flavored carbohydrate-electrolyte solution, they voluntarily drank 91% more than with unflavored water. Finally, such consumption of carbohydrate-electrolyte solution was sufficient to prevent voluntary dehydration during 180-min intermittent exercise in the heat.

Adolescent↗

A search for the cortical gustatory area in the hamster.

The gustatory area was searched in the cerebral cortex of the hamster by means of a combined approach using electrophysiological, behavioral, and histological experiments. The chorda tympani (CT), which innervates taste buds on the anterior part of the tongue, projected to a confined area anterior to the middle cerebral artery and just dorsal to the rhinal fissure. The trigeminal component of the lingual nerve (LN) area was located anterodorsal to the CT area, and the glossopharyngeal nerve (GN), which innervates taste buds on the posterior part of the tongue, was posterior to the CT area. The center of the CT and GN areas belonged to the dorsal part of the dysgranular insular cortex, and the LN area was within the primary somatosensory granular cortex. Bilateral symmetrical ablations of the CT and GN areas abolished the conditioned taste aversion (to sodium saccharin) that had been acquired before ablations, indicating a role of these areas in some cognitive processes of taste perception. Injections of horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) in the CT and GN areas, centered in the dysgranular insular cortex, revealed that this cortical region had major fiber connections with the contralateral homotypical cortical area, ipsilateral amygdala (central, lateral and basolateral nuclei), ipsilateral parvicellular part of the posteromedial ventral nucleus of the thalamus, bilateral parabrachial nucleus, contralateral nucleus of the solitary tract, raphe nuclei, and the locus ceruleus. Conversely, injections of WGA-HRP in these target areas showed anterograde and/or retrograde transport in the similar dysgranular insular cortex and additionally in the ventral part of the granular insular cortex. The present results suggest that the cortical gustatory area of the hamster is about 1.5 X 1.5 mm in size with the topographic organization between anterior and posterior parts of the tongue, and is located mainly in the dysgranular insular cortex around the middle cerebral artery.

Afferent Pathways↗

Retention of conditioned taste aversion to NaCl after chorda tympani transection in Fischer 344 and Wistar rats.

Fischer 344 (F344) rats fail to prefer sodium chloride (NaCl) solution to water, and this behavior is dramatically altered by bilateral transection of the chorda tympani nerve (CTX). Tests of retention and generalization of a conditioned taste aversion (CTA) to 0.15 M NaCl were used to assess alterations in salt taste perception after CTX. A CTA was established to 0.15 M NaCl in groups of F344 and Wistar rats after two pairings with LiCl (IP, 2% body weight; 0.15 M). After conditioning, animals received bilateral CTX or sham operations. Approximately 2 weeks after surgery animals were tested for retention of the CTA. Aversion to 0.15 M NaCl was evident in CTX and SHAM rats that had been conditioned prior to surgery, with no apparent difference in magnitude as a function of surgical condition. Thus, although CTX profoundly alters F344 rats' hedonic response to NaCl, it does not alter perceptual characteristics so markedly that NaCl is no longer recognized as the stimulus presented during aversion conditioning. Rather these studies suggest that in both the F344 and Wistar strains the chorda tympani nerve is not necessary for retention of a presurgical CTA to NaCl. These studies, therefore, do not provide evidence of changes in NaCl perceptual "quality" as a consequence of CTX either in F344 rats, where such changes were indicated by the preference data, or in the Wistar rat, where they were not.

Afferent Pathways↗

Propafenone versus disopyramide: a double-blind randomized crossover trial in patients presenting chronic ventricular arrhythmias.

In vitro and in vivo electrophysiological studies have shown that propafenone could be classified as a class I antiarrhythmic agent. The aim of this study was to investigate the short-term antiarrhythmic efficacy and safety of propafenone in 10 patients compared to disopyramide in a double-blind randomized protocol. Included patients suffered from ventricular arrhythmias with at least 60 ventricular premature beats (VPB) per hour refractory to at least two other antiarrhythmic agents. At the end of the control period and of the two treatment periods during which patients received either propafenone (300 mg three times a day) or disopyramide (200 mg three times a day), clinical examination, Holter recordings, electrocardiogram, and clinical laboratory tests were performed. The PR interval and the QRS interval were significantly increased with propafenone, but not with disopyramide. The cQT interval was not significantly changed by either propafenone or disopyramide. Heart rate was decreased with propafenone (p less than 0.05) with no change in the diurnal/nocturnal circadian ratio variation. Heart rate was significantly decreased with disopyramide only during the day. Five of nine patients in the propafenone group and two of nine patients in the disopyramide group showed a reduction in ventricular premature beats greater than 80%. Total resolution of severe arrhythmias (repetitive events) was seen in 5 of 8 patients with propafenone; 2 of 8 with disopyramide. Adverse events, when they occurred, were mild (visual disturbances, epigastric discomfort, changes in taste perception, transient atrioventricular block with propafenone, and photophobia with disopyramide), and did not require reduction or discontinuation of study drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Molecular cloning of a DEG/ENaC sodium channel cDNA from human testis.

The number of members of the recently defined DEG/ENaC sodium channel superfamily is increasing. Their importance in Na transport, taste perception, acid sensing, and mechanotransduction has been implicated. We have cloned a new member of this superfamily from human testis, which was named hTNaC1 (for human testis sodium channel 1). The hTNaC1 has 532 amino acid residues with two hydrophobic transmembrane domains. It has the highest identity (82%) with a rat H(+)-gated Na channel specific for sensory neurons (DRASIC) and a low identity (29%) with an epithelial isoform (alpha-ENaC) of this superfamily. Northern blot of human tissues revealed its selective expression in testis (7 kb) and absence in other tissues. The identification of a new member of Na channel specifically expressed in testis will expand the role of this channel family to the reproduction physiology.

Acid Sensing Ion Channels↗