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Pineal involvement in the alimentary behavior and taste preferences in the rat.

The purpose of this experiment was to explore the effects of pinealectomy or sham pinealectomy on circadian rhythms of taste preferences, food and fluid intake and body weight gain in rats. We compared the body weight gain, the amounts of food eaten and that of deionized water, total fluid, salt, sour, sweet and bitter near-threshold solutions consumed by rats before all surgical manipulations and after pinealectomy or sham pinealectomy. The results showed that the pineal gland does not exert a major influence on circadian organization of taste preferences, drinking, feeding and body weight modifications in the rat. The failure of pinealectomy to modify light/dark rhythms of taste preferences and other related alimentary behaviors may be explained by the fact that pinealectomy does not completely eliminate circulating melatonin.

Animals↗

The neurophysiology of taste and olfaction in primates, and umami flavor.

To investigate the neural encoding of glutamate (umami) taste in the primate, recordings were made from taste responsive neurons in the cortical taste areas in macaques. Most of the neurons were in the orbitofrontal cortex (secondary) taste area. First, it was shown that there is a representation of the taste of glutamate which is separate from the representation of the other prototypical tastants sweet (glucose), salt (NaCl), bitter (quinine) and sour (HCl). Second, it was shown that single neurons that had their best responses to sodium glutamate also had good responses to glutamic acid. Third, it was shown that the responses of these neurons to the nucleotide umami tastant inosine 5'-monophosphate were more correlated with their responses to monosodium glutamate than to any prototypical tastant. Fourth, concentration response curves showed that concentrations of monosodium glutamate as low as 0.001 M were just above threshold for some of these neurons. Fifth, some neurons in the orbitofrontal region, which responded to monosodium glutamate and other food tastes, decreased their responses after feeding with monosodium glutamate to behavioral satiety, revealing a mechanism of satiety. In some cases this reduction was sensory-specific. Sixth, it was shown in psychophysical experiments in humans that the flavor of umami is strongest with a combination of corresponding taste and olfactory stimuli (e.g., monosodium glutamate and garlic odor). The hypothesis is proposed that part of the way in which glutamate works as a flavor enhancer is by acting in combination with corresponding food odors. The appropriate associations between the odor and the glutamate taste may be learned at least in part by olfactory to taste association learning in the primate orbitofrontal cortex.

Animals↗

The representation of umami taste in the taste cortex.

To investigate the neural encoding of glutamate (umami) taste in the primate, recordings were made from taste-responsive neurons in the cortical taste areas in macaques. Most of the neurons were in the orbitofrontal cortex (secondary) taste area. First, it was shown that there is a representation of the taste of glutamate that is separate from the representation of the other prototypical tastants, sweet (glucose), salt (NaCl), bitter (quinine) and sour (HCl). Second, it was shown that single neurons that had their best responses to sodium glutamate also had good responses to glutamic acid. Third, it was shown that the responses of these neurons to the nucleotide umami tastant inosine 5'-monophosphate were more correlated with their responses to monosodium glutamate than to any prototypical tastant. Fourth, concentration-response curves showed that concentrations of monosodium glutamate as low as 0.001 mol/L were just above threshold for some of these neurons. Fifth, some neurons in the orbitofrontal region which responded to monosodium glutamate and other food tastes, decreased their responses after feeding with monosodium glutamate to behavioral satiety, revealing a mechanism of satiety. In some cases, this reduction was sensory-specific. Sixth, it was shown in psychophysical experiments in humans that the flavor of umami is strongest with a combination of corresponding taste and olfactory stimuli (e.g., monosodium glutamate and garlic odor). The hypothesis is proposed that part of the way in which glutamate works as a flavor enhancer is by acting in combination with corresponding food odors. The appropriate associations between the odor and the glutamate taste may be learned at least in part by olfactory to taste association learning in the primate orbitofrontal cortex.

Animals↗

The symptoms of hyperglycaemia in people with insulin-treated diabetes: classification using principal components analysis.

BACKGROUND AND AIMS: People with insulin-treated diabetes commonly experience symptoms of hyperglycaemia, but the nature of these symptoms and their origins are poorly understood. The aims of this study were (1) to identify and classify the symptoms of hyperglycaemia experienced by people with insulin-treated diabetes and (2) to identify patient characteristics associated with intensity of, and glycaemic threshold for, glycaemic symptoms. METHODS: Common hyperglycaemic symptoms were identified from preliminary interviews. Eighteen symptoms were used in a questionnaire. Four hundred participants estimated the intensities with which they experienced these symptoms during hyperglycaemia. Principal components analysis (PCA) was used to examine correlations between symptoms. Associations between symptom intensity, glycaemic threshold, and other characteristics were examined with multiple regression. RESULTS: In total, 361 participants (90.2%) reported experiencing hyperglycaemic symptoms. PCA suggested four symptom groupings: (1) feeling tense, irritability, restlessness, poor concentration (agitation) (2) thirst, dry mouth, need to urinate, not feeling right, sweet/funny taste, weakness (osmotic) (3) dizziness, blurred vision, light-headedness, weakness (neurological) (4) headache, nausea (malaise). Mean symptom intensity was associated with younger age. The median (range) estimated blood glucose threshold for symptom onset was 15 (8-30) mmol/L; there was a weak tendency for this threshold to be elevated in people who had impaired hypoglycaemia awareness. CONCLUSIONS: People with insulin-treated diabetes commonly reported symptoms associated with hyperglycaemia. PCA separated these into four groups. Osmotic symptoms appear to be specific to hyperglycaemia; symptoms in the other groups may suggest underlying physiological mechanisms, but are relatively non-specific. Symptoms are more intense in younger people and may be reported at lower blood glucose concentrations in people with normal awareness of hypoglycaemia.

Adolescent↗

Age-dependency of analgesia elicited by intraoral sucrose in acute and persistent pain models.

Treatment of pain in newborns is associated with problematic drug side effects. Previous studies demonstrate that an intraoral infusion of sucrose and other sweet components of mother's milk are effective in alleviating pain in infant rats and humans. These findings are of considerable significance, as sweet tastants are used in pain and stress management in a number of clinical procedures performed in human infants. The ability of sweet stimuli to induce analgesia is absent in adult rats, suggesting that this is a developmentally transient phenomenon. However, the age range over which intraoral sucrose is capable of producing analgesia is not known. We investigated the effects of intraoral sucrose (7.5%) on nocifensive withdrawal responses to thermal and mechanical stimuli in naive and inflamed rats at postnatal days (P) P0-21. In some rats, Complete Freund's adjuvant (CFA) was injected in a fore- or hindpaw to produce inflammation. In non-inflamed animals, for noxious thermal stimuli, sucrose-induced analgesia emerged at P3, peaked at P7-10, then progressively declined and was absent at P17. For mechanical forepaw stimuli, sucrose-induced analgesia emerged, and was maximal at approximately P10, then declined and was absent at P17. By contrast, maximal sucrose-induced analgesia for mechanical hindpaw stimuli was delayed (P13) compared to that for the forepaw, although it was also absent at P17. In inflamed animals, sucrose reduced hyperesthesia and hyperalgesia assessed with mechanical stimuli. Sucrose-induced analgesia in inflamed animals was initially present at P3 for the forepaw and P13 for the hindpaw, and was absent by P17 for both limbs. Intraoral sucrose produced significantly greater effects on responses in fore- and hindpaws in inflamed rats than in naive rats indicating that it reduces hyperalgesia and allodynia beyond its effects on responses in naive animals. These findings support the hypothesis that sucrose has a selective influence on analgesic mechanisms and that an enhanced sucrose effect takes place in hyperalgesic, inflamed animals as compared to naive animals. Taken together, these results indicate that intraoral sucrose alleviates transient pain in response to thermal and mechanical stimuli, and also effectively reduces inflammatory hyperalgesia and allodynia. Sucrose-induced analgesia is age-dependent and limited to the pre-weaning period in rats. The age-dependency of sucrose-induced analgesia and its differential maturation for the fore- and hindpaw may be due to developmental changes in endogenous analgesic mechanisms and developmental modulation of the interaction between gustatory and pain modulatory pathways.

Acute Disease↗

Application of hydrophilic interaction liquid chromatography/comparative taste dilution analysis for identification of a bitter inhibitor by a combinatorial approach based on Maillard reaction chemistry.

Activity-directed fractionation of heated carbohydrate/alanine solutions recently led to the discovery of (+)-(S)-1-(1-carboxyethyl)-5-hydroxy-2-(hydroxymethyl)pyridinium inner salt (1, alapyridaine), and it has been shown that this compound lowers the detection thresholds of sugars, glutamate, and NaCl solutions, whereas no influence on bitter perception was observed. As this class of Maillard-derived pyridinium betaines seemed to be promising targets for further research on their taste modulatory activity, the objective of the present investigation was to screen for bitter taste-suppressing target molecules in combinatorial libraries of pyridinium betaines prepared from 5-(hydroxymethyl)furan-2-aldehyde and amino acid mixtures by use of Maillard-type reaction chemistry instead of synthesizing and purifying each derivative individually. By application of hydrophilic interaction liquid chromatography in combination with the recently developed comparative taste dilution analysis, followed by structure determination, synthesis, and sensory studies, we have now succeeded in identifying 1-carboxymethyl-5-hydroxy-2-hydroxymethylpyridinium inner salt (2) as a potential bitter-suppressing candidate. While tasteless on its own, 2 was found to reduce the bitterness of various bitter tastants such as the amino acid L-phenylalanine, the peptide Gly-Leu, the alkaloid caffeine, and the bitter glycosides salicin and naringin.

Alanine↗

Acetaminophen self-administered in the drinking water increases the pain threshold of rats (Rattus norvegicus).

Previous studies have suggested that the addition of flavored acetaminophen suspension (for example, Children's Tylenol) in the drinking water of rats may not be effective in producing postoperative analgesia because of low levels of consumption. However, these investigations neither measured analgesia nor compared the consumption by rats that had undergone surgery with that by unmanipulated rats. The present study reports that although unmanipulated rats naive to the taste of flavored acetaminophen do indeed drink significantly less of this liquid than tap water, they drank sufficient amounts of the acetaminophen-containing solution to significantly raise pain thresholds, as measured by the hot-plate test. Moreover, rats that had undergone surgery drank significantly more acetaminophen solution than did those that had no surgery. These data suggest that oral self-administration of flavored acetaminophen by rats may be an appropriate means to reduce pain.

Acetaminophen↗

Impaired pressure sensation in mice lacking TRPV4.

The sensation of pressure, mechanosensation, in vertebrates remains poorly understood on the molecular level. The ion channel TRPV4 is in the TRP family and is a candidate for a mechanosensitive calcium-permeable channel. It is located in dorsal root ganglia. In the present study, we show that disrupting the Trpv4 gene in mice markedly reduced the sensitivity of the tail to pressure and acidic nociception. The threshold to noxious stimuli and the conduction velocity of myelinated nerve responding to stimuli were also impaired. Activation of unmyelinated nerve was undetected. However, the mouse still retained olfaction, taste sensation, and heat avoidance. The TRPV4 channel expressed in vitro in Chinese hamster ovary cells was opened by low pH, citrate, and inflation but not by heat or capsaicin. These data identify the TRPV4 channel as essential for the normal detection of pressure and as a receptor of the high-threshold mechanosensory complex.

Animals↗

Taste responses to amino acids in the southern leopard frog, Rana sphenocephala.

Integrated taste recordings of the glossopharyngeal (IX) nerve innervating the tongue of the southern leopard frog were studied in response to various amino acids and quinine hydrochloride. Amino acids and quinine hydrochloride elicited primarily phasic taste responses. Acidic (L-aspartic and L-glutamic) and basic (L-lysine and L-arginine) amino acids, adjusted to pH8, were effective taste stimuli. All glossopharyngeal nerve twigs that responded to amino acid stimuli also responded to quinine; however, not all quinine-sensitive IX nerve bundles were responsive to amino acids. Electrophysiological thresholds for amino acids were estimated to be 2.5-10 mM, whereas threshold for quinine hydrochloride averaged approximately 10 microM.

Amino Acids↗

Isolation and structure of pulcherrimine, a novel bitter-tasting amino acid, from the sea urchin (Hemicentrotus pulcherrimus) ovaries.

A novel sulfur-containing amino acid, pulcherrimine, has been isolated as a bitter principle from ovaries of the sea urchin Hemicentrotus pulcherrimus. The structure was elucidated as 4-(2'-carboxy-2'-hydroxy-ethylthio)-2-piperidinecarboxylic acid by spectroscopic and chemical methods. Absolute stereochemistry was determined by NOE experiments and chiral HPLC analysis. Pulcherrimine exhibited bitterness with a threshold value of 0.306 mM.

Amino Acids, Sulfur↗

Taste responses to amino acids from facial nerve branches innervating oral and extra-oral taste buds in the channel catfish, Ictalurus punctatus.

Electrophysiological recordings were obtained from two branches of the facial nerve innervating oral and extra-oral taste receptive fields, respectively, in the channel catfish, Ictalurus punctatus. The results indicate that taste buds innervated by the ramus ophthalmicus superficialis (ros), innervating taste buds on the nasal barbel, and the ramus palatinus (rp), innervating taste buds on the anterior palate, have similar chemical specificities for amino acids. Among the amino acids tested, the most stimulatory compounds for both the ros and rp were L-alanine and L-arginine, having estimated electrophysiological thresholds of approximately 10(-9) M. Dose-response functions for amino acid stimuli recorded from both the ros and rp were power functions extending over 5 log units of stimulus concentrations. The general similarity in the nature of the taste input from spatially distinct gustatory areas supports a chemotactic role of the facial taste system in the channel catfish.

Adaptation, Physiological↗

Activity-guided identification of (S)-malic acid 1-O-D-glucopyranoside (morelid) and gamma-aminobutyric acid as contributors to umami taste and mouth-drying oral sensation of morel mushrooms (Morchella deliciosa Fr.).

Although morel mushrooms are widely used as tasty ingredients in savory dishes, knowledge of the key compounds evoking their attractive taste is still very fragmentary. In the present study, taste activity-guided fractionation of an aqueous morel extract by means of the recently developed taste dilution analysis (TDA) enabled the localization of several umami-like-tasting fractions as well as a fraction imparting an intense mouth-drying sensation to the oral cavity. Hydrophilic interaction liquid chromatography (HILIC), LC-MS, and amino acid analysis led to the successful identification of gamma-aminobutyric acid as the chemical inducer of the mouth-drying and mouth-coating oral sensations imparted by the morel extract. Besides the well-known umami-like taste contributors L-glutamic acid, L-aspartic acid, and succinic acid, an additional HILIC fraction was isolated and evaluated as tasting umami-like. LC-MS and NMR studies revealed that this fraction consisted of a mixture of (S)-malic acid 1-O-alpha-D-glucopyranoside and (S)-malic acid 1-O-beta-D-glucopyranoside, the structure of which could be successfully confirmed by independent synthesis. To the best of our knowledge, this morel-derived glycoside, which we named (S)-morelid, has previously not been reported in any food products. Sensory analysis of aqueous solutions of the compounds identified revealed threshold concentrations of 0.02 mmol/L for the mouth-drying effect of gamma-aminobutyric acid and 6.0 mmol/L for the umami-like, slightly sour taste of (S)-morelid.

Ascomycota↗

The clinical significance of electrophysiological measures of olfactory function.

AIM: To establish the detectability of olfactory event-related potentials (OERP) in relation to the results from psychophysical tests of olfactory function. METHODS: Fifty-nine men and 64 women (aged 19-89 years) participated all of whom presented themselves to a specialized "Smell and Taste Clinic" because of chemosensory complaints. Their olfactory function was assessed by means of psychophysical tests, e.g., assessment of odor threshold, odor discrimination, and odor identification, which were combined in a composite "Threshold Discrimination Identification" score ("TDI score"). OERP were obtained in response to the olfactory stimulant phenyl ethyl alcohol; their presence/absence was judged by a trained observer. Using logistic regression the TDI score was calculated in relation to the subjects' olfactory function at which the probability of the presence of OERP became greater than chance. RESULTS: Based on psychophysical tests, 40 subjects were diagnosed with functional anosmia, 40 with hyposmia, and 43 subjects scored within the normal range. Causes of hyposmia and anosmia included congenital anosmia, Parkinson's disease, head trauma, infections of the upper respiratory tract, and sinunasal disease. A TDI score of 22.6 equivalent to "pronounced hyposmia" was identified as the turning point at which the probability of detection of OERP was higher than 50%. Its 95% confidence interval of 16.1-27.8 well reflected the range of hyposmia, i.e., was above significant loss of olfactory function (functional anosmia, TDI score<15.5) and below normal olfactory function (TDI score>30.5). CONCLUSION: The present results indicate that the probability to detect an OERP becomes greater than 50% within a range of olfactory function that separates functional anosmia from normosmia. Presence of OERP clearly signifies presence of olfactory function while this is not always the other way around with absence of OERP.

Adult↗

Brain mitochondrial aldehyde dehydrogenase: relation to acetaldehyde aversion in low-alcohol-drinking (UChA) and high-alcohol-drinking (UChB) rats.

Previous reports indicate that the low-drinker (UChA) rats, when compared to high-drinker (UChB) rats, display lower mitochondrial aldehyde dehydrogenase (ALDH2) activity due to a mutation of the Aldh2 gene. Because a later study found line differences in sensitivity to the aversive effects of acetaldehyde (AcH) administered intraperitoneally (i.p.), which were not associated with the line difference detected in blood AcH levels, the present study examined the contribution of brain ALDH2 activity to AcH aversion in UChA and UChB rats. In experiment 1, we established the dose - response curves for AcH aversion (25, 50 or 100 mg/kg i.p.) in rats of both lines by using a conditioned taste aversion (CTA) paradigm. The results confirm our previous finding that UChA and UChB rats presented marked differences in their AcH aversion thresholds, which were not associated with the line differences detected in blood AcH levels. In experiment 2, the possibility that the inhibition of the brain ALDH2 would lower the AcH aversion threshold in both lines was studied by determining the effect of cyanamide (10 mg/kg i.p.) pretreatment, an inhibitor of ALDH, on AcH aversion, blood AcH levels and brain ALDH2 activity. The finding that blocking the brain ALDH2 (52%) by cyanamide can make a non-aversive dose of AcH (25 mg/kg) aversive to UChA and UChB rats at blood AcH levels comparable to those induced by a non-aversive dose of AcH (100 mg/kg) in control UChB rats indicates that the line difference in AcH aversion is associated more with brain ALDH2 activity than with liver ALDH2 activity.

Acetaldehyde↗