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Oral etonitazene and cocaine consumption by AA, ANA and Wistar rats.

It has been previously suggested that drug-seeking behavior maintained by alcohol, opioids, and cocaine may have some common genetic determinants. Therefore, the present study examined the intake of etonitazene, a potent opioid agonist, and cocaine by alcohol-preferring AA (Alko, Alcohol), alcohol-avoiding ANA (Alko, Non-alcohol), and Wistar rats in a two-bottle choice test. The animals, housed in single cages, were given a choice between tap water and ascending concentrations of etonitazene (0.5, 1.0, 2.0, and 4.0 micrograms/ml) or cocaine (0.2, 0.4, 0.8, and 1.6 mg/ml) solutions prepared in water. Finally, to assess the sensitivity to bitter taste by these strains, a quinine preference test with ascending quinine concentrations was conducted. The clearest line differences were found with etonitazene: at all concentrations, the AAs consumed significantly more etonitazene than the ANAs and Wistars that showed no differences. The highest etonitazene intake by the AAs, 181 micrograms/kg/day at the concentration of 4.0 micrograms/kg, produced apparent signs of opioid intoxication and withdrawal. The AAs also drank more cocaine solution than the other lines. Since, however, the pattern of cocaine intake as a function of concentration resembled that with quinine, the line differences in cocaine consumption may partly be accounted for by the differential sensitivity to bitter taste by the lines. In contrast, the marked line differences in the intake of the etonitazene solutions, which had only a slightly bitter taste, seem more likely to have been produced by the post-ingestional effects of the opioid.

Alcohol Drinking↗

[Investigation about the taste of di, tri- and tetrahydroxy fatty acid].

Two diastereomeric 9, 10-dihydroxystearic acids, four diasteromeric 9,10,12-trishydroxystearic acids, a mixture of diastereomeric 9,10,12,13-tetrahydroxystearic acids, a mixture of 9.12,13,-trihydroxy-10 trans- and 9,10,13-trihydroxy-11-trans-octadecenoic acids (tri-OH-mixture from lipoxygenase catalysis) and the hydrogenated tri-OH mixture were tested for bitter taste. Only the tri - and tetrahydroxy acids are bitter. The taste thresholds of the saturated tri- and tetrahydroxy acids are in the range from 1.0--4.3 micron ol/ml. There are no significant differences in the taste thresholds between the four diastereomeric 9,- 10,12-trihydroxy acids. The double bond in the trihydroxy acids from the lipoxygenase catalysis enhances the bitter taste 3-fold.

Humans↗

Training and characterization of a quinine taste discrimination in rhesus monkeys.

There is a limited amount of information available about taste as a discriminative stimulus in non-human primates. The objective of this study was to establish a bitter taste (quinine sulfate) as a cue for lever selection and food reward in rhesus monkeys. Training took place in a series of steps that culminated in a schedule in which five lip contacts on a spout produced either quinine solution or water, followed by an opportunity to earn a food pellet by completing 20 presses on one of two levers. Responses on one of the levers resulted in food delivery if the solution contained quinine; responses on the other lever resulted in food delivery if the solution was water. A single session consisted of 100 randomly ordered taste trials with a 60-s interval between each trial. All of the animals acquired the discrimination, and the lowest quinine concentration that maintained consistent behavior was 0.3 mg/ml. To assess the specificity of the discrimination, compounds from other human taste categories were tested. A series of compounds that are detected as "bitter" by humans (caffeine, 1.5x10(-3) M; strychnine, 9x10(-4) M; PTC, 6x10(-5) M, denatonium benzoate, 2.24x10(-4) M; and urea, 3.0x10(-1) M) produced full generalization to the quinine sulfate discriminative stimulus, while "sweet" (sucrose, 2.9x10(-2) M) and "salty" (sodium chloride, 1.4 M) stimuli did not. There was individual variation among animals in response to "sour" compounds; acetic acid did not generalize to quinine, but HCl acid produced full generalization in one of three animals. These results suggest that a "bitter" taste cue is controlling the quinine discrimination.

Acetic Acid↗

Molecular cloning of a putative divalent-cation transporter gene as a new genetic marker for the identification of Lactobacillus brevis strains capable of growing in beer.

Random amplified polymorphic DNA (RAPD) PCR analysis of Lactobacillus brevis isolates from breweries revealed that one of the random primers could distinguish beer-spoilage strains of L. brevis from nonspoilage strains. The 1.1-kb DNA fragment amplified from all beer-spoilers included one open reading frame, termed hitA (hop-inducible cation transporter), which encodes an integral membrane protein with 11 putative trans-membrane domains and a binding protein-dependent transport signature of a non-ATP binding membrane transporter common to several prokaryotic and eukaryotic transporters. The hitA polypeptide is homologous to the natural resistance-associated macrophage protein (Nramp) family characterized as divalent-cation transport proteins in many prokaryotic and eukaryotic organisms. Northern blot analysis indicated that the hitA transcripts are expressed in cells cultivated in MRS broth supplemented with hop bitter compounds, which act as mobile-carrier ionophores, dissipating the trans-membrane pH gradient in bacteria sensitive to the hop bitter compounds by exchanging H+ for cellular divalent cations such as Mn2+. This suggests that the hitA gene products may play an important role in making the bacteria resistant to hop bitter compounds in beer by transporting metal ions such as Mn2+ into cells that no longer maintain the proton gradient.

Amino Acid Sequence↗

Debittering effect of Monascus carboxypeptidase during the hydrolysis of soybean protein.

The actions of pepsin and the admixture of pepsin and Monascus pilosus carboxypeptidase 1 (MpiCP-1) on the hydrolysis of soybean protein were studied. The results showed that the pepsin hydrolyzate of soybean protein was much more bitter and contained relatively smaller amounts of total free amino acids than the hydrolyzate obtained with the admixture of pepsin and MpiCP-1. In addition, hydrophilic and hydrophobic amino acids were present in almost equal proportions in the pepsin hydrolyzate, while mainly hydrophobic amino acids made up the hydrolyzate obtained with the admixture of pepsin and MpiCP-1. These results suggest that MpiCP-1 suppresses and reverses the development of the bitterness taste that results from the pepsin hydrolysis of soybean protein by releasing mainly hydrophobic amino acids from the C-termini of the bitter components.

Carboxypeptidases↗

The effect of amiloride on taste-evoked activity in the nucleus tractus solitarius of the rat.

Amiloride is an inhibitor of passive sodium transport. Its application to taste receptors blocks inward sodium current, suppresses sodium-induced neural activity and reduces the perceived intensity of NaCl. We recorded taste-evoked responses of single neurons in the nucleus tractus solitarius (NTS) of the rat before and after the lingual application of amiloride to determine which neurons would be affected, the degree of the effect and the subsequent form of the neural code for sodium. Responses to all 7 stimuli that contained Na+ or Li+ were suppressed by amiloride. Activity evoked by the 8 other stimuli was unaltered. NTS neurons could be divided into 4 subsets according to their response profiles: Group 1 (salt-sugar), Group 2 (salt), Group 3 (salt-acid) and Group 4 (acid-salt-bitter). The entire effect of amiloride was discharged on cells in Groups 1 and 2; those in Groups 3 and 4 were unaffected. Following amiloride application, the neural code for sodium and lithium salts was highly similar to those for acids, bitter salts and quinine. Thus the activity of neurons in Groups 1 and 2 may be responsible for the distinction between 'saltiness' and sour-bitter tastes. The results imply that specific receptors are responsible for the recognition and transduction of sodium salts and that this specificity is maintained in the peripheral taste nerves to be manifested in the NTS.

Amiloride↗

High sensitivity of the turtle olfactory system to nonvolatile substances: comparison of response properties with those in gustatory systems.

The olfactory responses of the aquatic turtles, Geocylemys reevesii whose nostrils are closed underwater to nonvolatile substances were measured by recording the olfactory bulbar responses. Various salts, acids and bitter substances elicited large responses, while sugars and amino acids did not elicit the responses. The thresholds for the salts were much lower than those of corresponding salts in the rat gustatory system. The responses to the salts were partially suppressed by amiloride. Various acids induced large responses and the magnitudes greatly depended on the anion species. The thresholds for the bitter substances were much lower than those of corresponding substances in the taste systems. Similar to the responses in taste systems, both electrostatic and hydrophobic interactions contribute to the binding of the substances to the receptor membranes. Similar to the taste systems, the response to quinine hydrochloride showed a sharp temperature dependence having a peak around 25 degrees C, while the responses to odorants did not show such peak. The present results suggest that the olfactory system has similar abilities to respond to salts, acids and bitter substances to those in gustatory systems and that the high sensitivity of the olfactory system to chemical stimuli is not only attributable to the second messenger amplification system, but also to the basic property of the receptor membrane independent of the amplification system.

Acids↗

Dietary quinine reduces body weight and food intake independent of aversive taste.

Separate groups of rats were chronically fed diets adulterated with either bitter tasting quinine sulfate (QSO4), equal amounts of quinine in the less bitter form of quinine tannate (QT), or an amount of sucrose octaacetate (SOA) determined to have aversive taste properties equal to the QSO4 diet. Dietary adulteration with SOA did not affect food intake or body weight. Dietary adulteration with quinine resulted in an initial reduction in food intake that showed a relative recovery but remained depressed compared to the intake of a group eating a quinine-free diet. Ingestion of diets containing equal amounts of quinine base resulted in equivalent chronic body weight reductions, despite different aversive diet characteristics. These results suggest that bitter taste is not the significant variable underlying the body weight effects of quinine but that quinine exerts some postingestive effect on body weight mediated by a slight but sustained decrease in the level of energy intake.

Animals↗

Effects of body weight loss and taste on VMH-LH electrical activity of rats.

Electrical responses of ventromedial (VMH) and lateral (LH) hypothalamus to graded decrease in body weight and to taste were recorded from a conscious rat with chronically implanted macroelectrodes. Graded reduction in body weight was correlated with gradual increase in LH activity and reciprocal decrease in VMH activity, both of which were stable and specific to each gradation in body weight. On gustation of any test solution, basal activity was temporarily altered, if any. On sweet taste of calorically rich sucrose, VMH activity was enhanced and LH showed decrease. But on sweet taste of calorically inert saccharin, VMH activity was increased, though a reciprocal decrease in LH was not shown. Contrastingly, both bitter taste and salt taste caused increased LH activity but no change in VMH activity. Enhanced VMH activity correlated with sweet taste may be due to activation of VMH glucoreceptors. LH activation correlated with bitter and salt taste is a likely response of two distinct groups of LH units; one responding to salt taste and the other to bitter aversive taste.

Animals↗

Effect of lipid-derived second messengers on electrophysiological taste responses in the gerbil.

Integrated chorda tympani (CT) recordings were made to salty, sour, sweet, bitter, and glutamate tastants before and after a 4-min application of modulators of lipid-derived second messenger systems. The modulators included two membrane-permeable analogues of DAG, 1-oleoyl-2-acetyl glycerol (OAG) and dioctanoyl glycerol (DiC8); thapsigargin, which releases Ca++ from intracellular stores; ionomycin, a calcium ionophore; lanthanum chloride, an inorganic calcium channel blocker; nifedipine, a dihydropyridine calcium channel blocker; quinacrine diHCl, a phospholipase A2 antagonist; melittin, a phospholipase A2 agonist; and indomethacin, which decreases the release of prostaglandins by inhibiting the enzyme cyclo-oxygenase. The main findings were: OAG (125 microM) and DiC8 (100 microM) blocked the responses of several bitter compounds while enhancing the taste response to several sweeteners. Lanthanum chloride blocked all responses, which may be due to the fact that it blocks tight junctions. Quinacrine (1 mM) suppressed several bitter responses while enhancing the response to several sweeteners. The enhancement of sweet taste responses by DAG analogues suggests that there is cross-talk between the adenylate cyclase system and one (or more) pathways involving lipid-derived second messengers in taste cells.

Animals↗

Modulators of the adenylate cyclase system can alter electrophysiological taste responses in gerbil.

The adenylate cyclase system has been implicated in taste transduction. The purpose of this study was to determine whether application of modulators of the adenylate cyclase system to the tongue alter taste responses. Integrated chorda tympani (CT) recordings were made in gerbils to bitter, sweet, salty, sour, and glutamate tastants before and after a 4-min application of four types of modulators of the adenylate cyclase system. The four types of modulators tested were: a) NaF, a compound that promotes dissociation of GTP binding protein; b) forskolin, a powerful stimulant of adenylate cyclase; c) 8-bromoadenosine 3' :5'-cyclic monophosphate sodium salt (8BrcAMP) and N6,2'-O-dibutyryl-adenosine 3' :5'-cyclic monophosphate sodium salt (DBcAMP), two membrane permeable forms of cAMP; and d) 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) and N-(2-[methylamino]ethyl)-5-isoquinolinesulfonamide dihydrochloride) (H-8), which are protein kinase inhibitors. The tast compounds tested were: NaCl (30 mM), monosodium glutamate-MSG (50 mM), sucrose (30 mM), HCl (5 mM and 10 mM), KCl (300 mM), quinine HCl (30 mM), MgCl2 (30 mM), erythromycin (0.7 mM and 1 mM), HCl (5 mM and 10 mM), and urea (2 M). The main findings were as follows. NaF (20 mM) significantly inhibited responses to bitter compounds up to 35% and enhanced the response to sucrose by 30%. NaCl (20 mM), used as a control for NaF, inhibited most responses up to 78% with no enhancement of sucrose as seen with NaF. 8BrcAMP (1.16 mM) reduced the responses to bitter-tasting quinine HCl, MgCl2, and erythromycin but not to urea.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Use and perceived attributes of cruciferous vegetables in terms of genetically-mediated taste sensitivity.

Bitter tasting compounds in cruciferous vegetables resemble chemically the compound phenylthiocarbamide (PTC). As sensitivity to PTC is genetically mediated, it was hypothesized that this characteristic would be linked to greater sensitivity of the bitter tasting components in cruciferous vegetables, and that PTC sensitivity would be reflected in less favourable sensory perceptions and lower use of the vegetables. PTC status was determined for healthy, racially and culturally similar women, alike in foodways and aged 18-46 years. The frequency of use and perceptions of sensory, post-ingestional and social attributes of 11 cruciferous and two non-cruciferous vegetables in both raw and cooked forms were compared between the PTC tasters and non-tasters. Minimal effects of PTC status on these factors were observed. Only two vegetables showed significant differences in use--PTC non-tasters used cooked turnip and raw watercress significantly more than did PTC tasters. Perceived bitter taste and aroma did not offer an explanation for the findings. Similarly, familiarity, early exposure, and tolerance did not account for any group differences. PTC status, especially in terms of non-tasting propensity, may have some sensory-specific effects which will impact on the use of cruciferous vegetables by young and mature women, but environmental factors may offset this effect and must be considered in studies of food behaviour.

Adolescent↗

Toxicological studies on debitterized Neem oil (Azadirachta indica).

Azadirachta indica, popularly known as 'Neem' in India, is widely grown all over the tropics. The seed contains 45% oil and is a minor oil of considerable potential. Neem oil is bitter and inedible. Recently, a method has been developed to completely remove the bitter and odoriferous principles and leave a bitterless, odourless and colourless oil. The nutritional and chemical evaluation of debitterized neem oil (NO) was reported earlier (C. Rukmini, Food Chemistry 1987, 26, 119). We report here a three-generation study, carried out according to WHO/FDA protocol in groups of 15 male and 15 female rats fed a diet containing 10% NO or groundnut oil (GNO). Reproductive toxicology was monitored for three generations. The results obtained in both the matings in all the three generations did not show any adverse effects on the reproductive parameters studied in rats fed NO and were similar to those observed in rats fed GNO. The mean organ weights and the histopathological evaluation of all the organs were similar to those of the control (GNO-fed) rats. A mutagenicity test of NO was also found to be negative in Ames test as reported earlier (K. Polasa and C. Rukmini, Food and Chemical Toxicology 1987, 25, 763). These studies indicate that NO devoid of all the bitter and odoriferous principles, may be recommended as safe for consumption by humans.

Animals↗

Indigenous phytotherapy of gastrointestinal disorders in a lowland Mixe community (Oaxaca, Mexico): ethnopharmacologic evaluation.

Gastrointestinal disorders are one of the major health problems in developing countries. Sixty-five plants used popularly in the treatment of such disorders in a Mixe Indian community in Oaxaca (Mexico) and collected during a fieldstudy of 15 months are described. According to indigenous criteria a plant is used in the treatment of a certain illness because of the plant's characteristic smell and taste. Plants with astringent properties are particularly valued to treat diarrhoea and dysentery. Bitter, aromatic and bitter-aromatic plants are especially employed to treat gastrointestinal cramps and pain. Additionally, the efficacy of these plants was evaluated using ethnobotanical, phytochemical and pharmacologic information on the plants. The majority of the plants contain chemicals that may produce the effects desired by the Mixe. Frequently tannin-containing drugs are used to treat diarrhoea and dysentery. A large number of the plants used by the Mixe in the treatment of gastrointestinal pain contain essential oil or bitter principles. As a result of this evaluation, plants were selected which should be studied phytochemically and pharmacologically with priority, to evaluate further their potential in the treatment of gastrointestinal disorders.

Diarrhea↗

Differences in smoking-related variables based on phenylthiocarbamide "taster" status.

Test strips impregnated with phenylthiocarbamide (PTC) have been used to identify genetic differences based on whether a bitter taste is perceived. To determine whether smokers who perceive PTC as bitter tasting ("tasters") would differ from those who describe it as tasteless ("non-tasters") on smoking-related variables, we studied 464 current smokers (70% female, 79% White; mean age 30.5+/-9 years) recruited to participate in laboratory experiments and clinical trials. Of these, 217 (47%) reported the PTC strips as tasteless and 154 (33%) as tasting bitter. The remaining 93 (20%) described the taste as salty, sweet, or other and were excluded from further analyses. Comparing tasters with non-tasters, we found significant differences in mean (S.D.) total years smoked (14.5 [9.2] for non-tasters, vs. 12.6 [8.4] for tasters, p<.05), Fagerstrom Tolerance Questionnaire scores (6.4 [2.1] vs. 5.8 [2.1], p<.01), and scores on the Positive Reinforcement scale of the Michigan-Nicotine Reinforcement Questionnaire (8.1 [2.9] vs. 6.8 [3.1], p<.05). Results suggest that among smokers, ability to taste PTC may confer some protection from development of nicotine dependence and positive reinforcement from smoking.

Adult↗

Application of rotary microfiltration in debittering process of spent brewer's yeast.

This study concerns the production of yeast extract from spent brewer's yeast using rotary microfiltration as a means to combine debittering and cell debris separation into a single step, without using a toxic alkali wash. The pH of yeast homogenate was found to affect protein yield and bitterness of the product. Rotary filtration of yeast homogenate at various pHs resulted in different percent protein transmissions. These were found to be 5.05%, 9.83%, and 30.83% for pH 5, 6, and 7.5, respectively. The bitterness concentration in the permeate was also found to be higher at higher pHs. Autolysis of the cell homogenate prior to filtration increased protein yield and decreased bitterness considerably. At pH 5.5, the protein transmission was increased to 60% and debittering efficiency was increased from 59% to 86%. The permeate flux and protein productivity could be further increased by increasing the rotational speed, but this resulted in a decrease in debittering efficiency. Thus, the rotational speed should be carefully selected to compromise between the yield and product quality. Furthermore, for the tested rotational speeds of 600 and 1000 rpm, the change in feed flow rate from 11 to 35 L h(-1) changes the flow behavior from turbulent vortex flow to laminar vortex flow, thus decreasing the flux and protein productivity.

Hydrogen-Ion Concentration↗

Enzymatic debittering of food protein hydrolysates.

Protein hydrolysates have a range of applications in the food and allied healthcare sectors. Bitterness is a negative attribute associated with most food protein hydrolysates. The development of biotechnological solutions for hydrolysate debittering is ongoing. Specific enzymatic debittering strategies have focused on the application of proline specific exo- and endopeptidases given the contribution of proline residues to peptide/hydrolysate bitterness. Hydrolysate manufacturing conditions may also play an important role in bitterness development. Practical solutions to hydrolysate debittering are likely to involve judicious choice of enzymatic processing conditions in conjunction with the use of peptidase activities having targeted hydrolytic specificity.

Aminopeptidases↗

Taste perception and coding in Drosophila.

BACKGROUND: Discrimination between edible and contaminated foods is crucial for the survival of animals. In Drosophila, a family of gustatory receptors (GRs) expressed in taste neurons is thought to mediate the recognition of sugars and bitter compounds, thereby controlling feeding behavior. RESULTS: We have characterized in detail the expression of eight Gr genes in the labial palps, the fly's main taste organ. These genes fall into two distinct groups: seven of them, including Gr66a, are expressed in 22 or fewer taste neurons in each labial palp. Additional experiments show that many of these genes are coexpressed in partially overlapping sets of neurons. In contrast, Gr5a, which encodes a receptor for trehalose, is expressed in a distinct and larger set of taste neurons associated with most chemosensory sensilla, including taste pegs. Mapping the axonal targets of cells expressing Gr66a and Gr5a reveals distinct projection patterns for these two groups of neurons in the brain. Moreover, tetanus toxin-mediated inactivation of Gr66a- or Gr5a-expressing cells shows that these two sets of neurons mediate distinct taste modalities-the perception of bitter (caffeine) and sweet (trehalose) taste, respectively. CONCLUSION: Discrimination between two taste modalities-sweet and bitter-requires specific sets of gustatory receptor neurons that express different Gr genes. Unlike the Drosophila olfactory system, where each neuron expresses a single olfactory receptor gene, taste neurons can express multiple receptors and do so in a complex Gr gene code that is unique for small sets of neurons.

Animals↗