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Lipid metabolic interrelationships and phospholipase activity in gustatory epithelium of Ictalurus punctatus in vitro.

The catfish, Ictalurus punctatus, is an important model for studying the biochemical mechanisms of taste at the peripheral level. The type, amount and metabolic activity of the lipids within this tissue play important roles in taste transduction by forming the matrix in which the receptors for taste stimuli are imbedded and by acting as precursors to second messengers. The metabolic interconversions that occur among the lipids on the taste organ (barbels) of this animal are reported here. When sodium [32P]phosphate was incubated with minced pieces of epithelium from the taste organ of I. punctatus, phospholipids became labeled. Maximal incorporation occurred near 20 min for lysophosphatidylcholines (LPC), phosphatidylcholines (PC) and phosphatidylinositols (PI). The phosphatidylethanolamines (PE) and phosphatidylserines (PS) became labeled more slowly. The label in LPC and PC declined from 20 min to 120 min, while that of the other fractions increased or was stable over the 20-120 min time period. Upon addition of 1,2-di-[1'-14C]palmitoyl-sn-glycero-3-phosphocholine to the medium, 14C was found within minutes in all of the phospholipids assayed. The amount of label incorporated increased with time, with maximum labeling for all phospholipids occurring at 15 min. However, 14C appeared predominantly first (by 5 min) in a neutral lipid fraction (fraction AG, consisting of free fatty acids, mono- and diglycerides, triglycerides and methyl esters), then declined rapidly as the phospholipids gradually incorporated more label. Within minutes of addition of 1-[1'-14C]palmitoyl-sn-glycero-3-phosphocholine (lysophosphatidylcholine) the 14C-label was detected in the neutral lipid fraction AG, then in the PC fraction, and later in the other phospholipids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antagonist-precipitated opioid withdrawal in rats: evidence for dissociations between physical and motivational signs.

In rats made opioid dependent by the implantation of a single morphine 75 mg base pellet, an attempt was made to determine whether any correlational existed between physical and motivational withdrawal signs by adjusting the dose of naloxone used to precipitate withdrawal. The models used to study motivational signs were taste (one- and two-bottle) conditioning and operant responding for food under an FR15 schedule of reinforcement. Naloxone at doses of 0.01 mg/kg and above produced both a conditioned taste aversion (two-bottle test only) and reduced food responding in morphine pellet, but not placebo pellet, implanted animals. No physical withdrawal signs, e.g., wet dog shakes, diarrhoea, were noted until naloxone doses of 0.05 mg/kg and above were used. It is concluded that the difference in naloxone doses required to elicit physical and motivational withdrawal components provides further support for their dissociation.

Animals↗

Back to the future: Valentin Magnan, French psychiatry, and the classification of mental diseases, 1885-1925.

To this day one of the most curious gaps in the historiography of French psychiatry is the era between the fin-de-siècle and the 1920s, years that overlapped the life and career of Valentin Magnan (1835-1916), a pivotal figure in the historical classification of mental diseases. This paper seeks to address this shortcoming as well as contribute to the growing scholarly interest in the history of clinical psychiatry. It argues that Magnan was in many ways a tragic figure, someone who lived and worked at a time when circumstances conspired against him and his efforts to reform psychiatric classification. Essentially Magnan had the misfortune to practise psychiatry when Emil Kraepelin's influence began to spread beyond Germany's borders, sparking a nationalist reaction that penalized both French Kraepelinians and Magnan whose theories shared similarities with Kraepelin's. But Magnan's stature also suffered because of the intense internecine quarrels that arose in late nineteenth-century French psychiatry. Magnan was no helpless victim, though, and there is reason to believe that some of the criticism directed at him was based on documented personal failings. Ultimately, Magnan's theory of psychiatric classification was overtaken by these and other events in French psychiatry, culminating by the interwar period in the emergence of a new national, nosological pardigm that has dominated French psychiatry for most of the twentieth century. Thus Magnan was in many respects a pariah within French psychiatry by the early twentieth century. An examination of his career casts light on this crucial turning-point in the history of French psychiatry and indicates why and how the new model of classification was more to the tastes of his medical colleagues.

Classification↗

Characterization of bitter taste responses of intestinal STC-1 cells.

Cellular responses of STC-1 cells to two bitter tastants (denatonium and caffeine) were investigated using a calcium-imaging technique and compared with the response to bombesin. Caffeine is known to stimulate taste receptor cells, but the properties of its signaling have not been well studied. STC-1 cells responded to all three molecules in a dose-dependent manner, and when a reverse transcriptase-polymerase chain reaction (RT-PCR) for denatonium receptor was performed, the product of predicted size was detected in STC-1 cells. Furthermore, all three signaling pathways were blocked by a phospholipase C (PLC) inhibitor, demonstrating the essential involvement of PLC in cellular responses. To study the regulatory system of G protein signaling in STC-1 cells, we searched G protein-coupled receptor kinases (GRKs) by the degenerate-primer PCR method and found that GRK2 is expressed. We also demonstrated that three GRKs (GRK2, GRK3 and GRK5) are differentially distributed in the circumvallate papilla while only GRK2 is present in taste bud cells. Finally, we overexpressed GRK2 in SCT-1 cells and found that bombesin-induced response was strongly inhibited by GRK2 but denatonium-activated signaling was not affected. In the case of caffeine, response was decreased by expression of GRK2 only when cells were activated by 1 mM caffeine. Thus, we showed that STC-1 cells emerge as a cell model for studying the molecular mechanism of bitter taste signaling, and could indicate properties of caffeine-induced signaling in comparison with other signaling.

Animals↗

Artificial neural networks estimate the contribution of taste neurons to coding.

Taste qualities are believed to be coded in the activity of populations of taste neurons. However, it is not clear whether all neurons are equally responsible for coding. To clarify the point the relative contribution of each taste neuron to coding was assessed by constructing simple three-layer neural networks with input neurons that represent cortical taste neurons of the rat. The networks were trained by the back-propagation learning algorithm to classify the neural response patterns to the basic taste stimuli (sucrose, HCl, quinine-hydrochloride, and NaCl). The networks had four output neurons representing the basic taste qualities, the values of which provide a measure for similarity of test stimuli to the basic taste stimuli. We estimated relative contributions of input neurons to the taste discrimination of the network by examining their significance S(j), which is defined as the sum of the absolute values of the connection weights from the jth input neuron to the hidden layer. When the input neurons with a smaller S(j) (e.g., 15 out of 39 input units) were "pruned" from the trained network, the ability of the network to discriminate the basic taste qualities was not greatly affected. On the other hand, the taste discrimination of the network progressively deteriorated much more rapidly with pruning of input neurons with a larger S(j). These results suggest that cortical taste neurons differentially contribute to the coding of taste qualities. Input neurons with a larger S(j) tended to be with a larger variation of neural discharge rates to the basic taste stimuli. The variation of neural discharges may be important in the coding of taste qualities.

Algorithms↗

Mice with a targeted disruption of the neurotrophin receptor trkB lose their gustatory ganglion cells early but do develop taste buds.

The alleged ability of taste afferents to induce taste buds in developing animals is investigated using a mouse model with a targeted deletion of the tyrosine kinase receptor trkB for the neurotrophin BDNF. This neurotrophin was recently shown to be expressed in developing taste buds and the receptor trkB has been shown to be expressed in the developing ganglion cells that innervate the taste buds. Our data show a reduction of geniculate ganglion cells to about 5% of control animals in neonates. Degeneration of ganglion cells starts when processes reach the central target (solitary tract) but before they reach the peripheral target (taste buds). Degeneration of ganglion cells is almost completed in trkB knockout mice before taste afferents reach in control animals the developing fungiform papillae. Four days later the first taste buds can be identified in fungiform papillae of both control and trkB knockout mice in about equal number and density. Many taste buds undergo a normal maturation compared to control animals. However, the more lateral and caudal fungiform papillae grow less in size and become less conspicuous in older trkB knockout mice. No intragemmal innervation can be found in trkB knockout taste buds but a few extragemmal fibers enter the apex and end between taste had cells without forming specialized synapses. Taste buds of trkB knockout mice appear less well organized than those of control mice, but some cells show similar vesicle accumulations as control taste bud cells in their base but no synaptic contact to an afferent. These data strongly suggest that the initial-development of many fungiform papillae and taste buds is independent of the specific taste innervation. It remains to be shown why others appear to be more dependent on proper innervation.

Animals↗

[Feeling like a snack. The influence of taste on our eating habits].

This article describes the physiological, social and emotional aspects of food. Human physiology determines 'the need' for food, society 'the possibilities' and our emotions 'the choice'. Grazing is becoming a common phenomenon in modern society: the frequent eating of snacks between meals, or even instead of meals. One of the consequences is an increasing dental risk, due to repeated acid attacks on the enamel. For a better understanding of these changing eating habits and the emotional values of food, the Dutch centre for the research of taste (CSO) has developed the so-called 'Taste-Cube'. This cube attaches human values to different types of food. The value of a product is created by the consumer, according to his 'internal logic'. In this article these concepts are explained.

Dental Caries↗

Functional decortication by cortical spreading depression does not prevent forced extinction of conditioned saccharin aversion in rats.

Conditioned taste aversion established in rats by association of saccharin drinking with subsequent lithium chloride intoxication decreased saccharin intake to 22% of normal consumption. Force-feeding saccharin to intact and functionally decorticate trained rats returned saccharin consumption on the next day to 62% (n equals 18) and 77% (n equals 19), respectively. Over-trained conditioned saccharin aversion was affected by forced extinction in a similar way (saccharin intake increased from 28% to 50% and 63%, respectively). Intact brain rats refused to swallow saccharin during forced feeding. while functionally decorticate animals showed no signs of aversion; but extinction was almost equal in both cases. Application of lithium chloride after forced feeding of saccharin in functionally decorticate rats neither prevented extinction of conditioned taste aversion nor reestablished the aversion habit extinguished earlier with intact brain. It is concluded that acquisition of the conditioned taste aversion requires cortical input to a short-term memory file, whereas decorticate extinction can be induced by subcortical gustatory processing analogous to the mechanism controlling feeding behavior during the preweaning period.

Animals↗

X-ray structures of new dipeptide taste ligands.

The molecular basis of sweet taste was investigated by carrying out the crystal state conformational analysis by X-ray diffraction of the following dipeptide taste ligands: N-3,3-dimethylbutyl-aspartylphenylalanine methyl ester, I (N-DMB-Asp-Phe-OMe), its sodium salt (N-DMB-Asp-Phe-ONa), II, aspartyl-D-2-aminobutyric acid-(S)-alpha-ethylbenzylamide, III (Asp-D-Abu-(S)-alpha-ethylbenzylamide), aspartyl-N'-((2,2,5,5-tetramethylcyclopentanyl)-carbonyl)-(R)- 1,1-diamino-ethane, IV (Asp-(R)-gAla-TMCP), and aspartyl-D-valine-(R)-alpha-methoxymethylbenzyl amide, V (Asp-D-Val-(R)-alpha-methoxymethylbenzylamide). With the exception of the sodium salt II, all compounds are sweet-tasting, showing in some cases considerable potency enhancement with respect to sucrose. The results of this study confirm the earlier model that an 'L-shape' molecular array is essential for eliciting sweet taste for dipeptide-like ligands. In addition, it was established that (i) substitution of the N-terminal group does not inhibit sweet taste, if its zwitterionic character is maintained; (ii) a hydrophobic group located between the stem and the base of the L-shape could be responsible for sweetness potency enhancement, as found in I, III and IV; in fact, the extraordinary potency of the N-alkylated analogue I would support a model with an additional hydrophobic binding domain above the base of the 'L'; (iii) removal of the methyl ester at the C-terminus of compound I with the salt formation gives rise to the tasteless compound II; (iv) for the first time all possible side-chain conformers (g-, g+ and t) for the N-substituted aspartyl residue were observed; and (v) a retro-inverso modification, incorporated at position 2 of the dipeptide chain, confers greater flexibility to the molecule, as demonstrated by the contemporary presence of six conformationally distinct independent molecules in the unit cell and yet sweet taste properties are maintained, as found in IV.

Computer Simulation↗

Effects of oral zinc loading on zinc metabolism in humans II: in vivo kinetics.

The effects of oral zinc loading on zinc metabolism were studied in 10 patients with taste and smell dysfunction following oral administration of Zn-65 (physical t1/2 = 245 d) and subsequent administration of oral stable zinc. Patients took an ad libitum dietary zinc intake of 8-13 mg daily for 290-440 days (mean, 336) following Zn-65 administration, followed by an intake of an additional 100 mg/day of zinc ion (as ZnSO4) over the next 112-440 days (mean, 307). A previously developed compartmental model, based on five day studies of patients with taste and smell dysfunction, was extended in such a way that it was consistent with both short term and long term kinetics. In this extended model, the turnover of 90% of total body zinc, previously unaccounted for by the kinetics in the short term studies could be explained by a single compartment, as postulated in the short term studies. Using the model, it was found that changes in the rate constants for gastrointestinal absorption and renal excretion of zinc were both necessary and sufficient to explain the changes seen in the kinetic curves following oral zinc loading. Michaelis-Menten type saturation mechanisms were adequate to explain the observed parameter changes. These changes also accounted for the observed mean plasma zinc mass increase of only 37% above pre-load levels in face of an 11-fold increase in zinc intake.

Administration, Oral↗

Physico-chemical studies of taste reception. IV. Response of individual phospholipid membrane to a variety of chemical stimuli.

Variations in the membrane potential across model membranes made of Millipore filter paper and various single phospholipids were measured in response to salt, acid and distilled water. The phospholipids used were phosphatidylcholine (c), spingomyelin (SM), phosphatidylethanolamine (PE), and phosphatidylserine (PS). Results were compared with those obtained with the model membrane made of the total lipids extracted from bovine tongue epithelium, which simulated well the receptor potential observed with intact tast organs. The membrane potential of PE- and PS-membranes increased monotonously with increase of the concentration of 1:1 type salt, while that of PC- and SM-membranes exhibited no appreciable change in 1:1 salt solutions. Application of CaC12 to the membranes brought about a varity of response depending on the species of lipids used. PE- and PS-membranes showed a larger change in the membrane potential than PC- and SM-membranes when pH of the solution was varied. Fe-3+ was strongly absorbed on the surface of PC and SM-membranes, while Fe-3+ bound to PE- and PS-membranes was easily removed by an application of salt solution. A transient increase in the membrane potential was observed when distilled water was applied to the membrane adapted to an appropriate salt solution, which was similar to the water response observed in taste cells. PC- and SM-membranes responded to water when the membrane adapted to either NaC1 or CaC12, but PS-membrane responded only when the membrane was adapted to a solution containing CaC12. PE-membrane did not respond to water in any cases examined. The membrane prepared with a mixture of two species of phospholipids responded neither to salt nor to water, while the membranes prepared with the total lipids or a mixture of three species of lipids in appropriate ratio responded to both. The water response of the total lipids membrane vanished in a high temperature medium, while the water response of PC-membrane retained in all temperature ranges examined, i.e. between 20 degrees and 62 degrees C. The results obtained suggest that a mosaic structure, where each domain has different functions against various chemical stimuli, is formed on the surface of the model membrane made of the total lipids.

Animals↗

Taste in the monkey cortex.

The sense of taste in humans differs substantially from that of rodents, from which a preponderance of gustatory electrophysiology derives. To establish a more appropriate neural model for human gustation, we recorded the activity of single neurons in the primary taste cortex in 11 alert cynomolgus macaques. Taste cells composed 6% of all neurons encountered. Another 24% responded during mouth and jaw movements, and 4% were sensitive to tactile stimulation of the mouth. Smaller numbers responded during olfactory or visual stimulation, or when the monkey extended his tongue. Taste cells could be divided into four statistically independent groups, corresponding to those most responsive to glucose (38%), NaCl (34%), quinine (22%), or HCI (5%). The location of a taste cell did not predict its response profile, i.e., there was no clear topographic organization of taste sensitivity. We established neural thresholds and intensity-response functions to the basic stimuli and determined that-with the exception of HCl, to which the macaque is relatively insensitive-they were similar to those reported by human subjects. We then turned to the coding of taste quality, as inferred in macaques from the patterns of neural activity elicited by each of greater than 100 stimuli. The results proved generally faithful to human reports of the perceived qualities of these same tastants. Finally, an investigation of taste mixtures revealed a degree of mixture suppression and interaction among basic qualities similar to those reported by humans. We conclude that the alert macaque offers a reliable neural model for human gustation.

Animals↗

Young children's food preferences: a comparison of three modalities of food stimuli.

Food preferences are widely agreed to be important determinants of eating behaviour in young children. Existing studies of methods of assessing preferences have suggested tasting and ranking foods can generate reliable responses with young children, but there have been few attempts to assess other methods which might provide a more convenient alternative in situations where the use of real foods could be difficult (e.g. outside the laboratory), or tasting could be undesirable (e.g. if there are large numbers of foods, or foods which children would be unwilling to taste). The present study is a comparison of the reliability of preferences measured using: (i) real foods; (ii) food photographs; and (iii) food models, in 3 to 5-year-old children. The results showed that the tasting method produced good results, replicating existing data from U.S. samples. Food photographs came a close second in reliability but food models produced unreliable rankings, especially in the youngest group. Five-year-olds produced significantly more consistent results than the younger children. These results indicate that using real foods as the stimuli produces the most reliable taste preferences with children in this young age range, but photographs may provide a convenient alternative with adequate reliability.

Age Factors↗

Nitric oxide modulates lithium-induced conditioned taste aversion.

Nitric oxide (NO) has been shown to affect the behaviour in animal models of depression, anxiety and avoidance learning. Lithium has marked effect in avoidance learning, an effect that can be modulated via the 5-HT system. Experiments were carried out using the conditioned taste aversion (CTA) paradigm to investigate whether administration of NO-modifying drugs, serotonergic drugs and lithium, alone or in combination, induced or affected a CTA. The NO-precursor L-arginine (L-Arg), the non-specific inhibitor of NOS and guanylate cyclase, methylene blue (MB) and the specific NOS inhibitor 7-Nitroindazole (7-NI) all produced CTAs in a dose-dependent fashion. Furthermore, we found that L-Arg counteracted the CTAs induced by LiCl or MB but failed to modulate the CTA produced by 7-NI. The administration of the selective 5-HT1A agonist, 8-OH-DPAT, counteracted the CTAs produced by MB and 7-NI. In contrast, depletion of 5-HT by p-Chlorophenylalanine did not affect the aversions produced by MB and 7-NI, but counteracted the CTA produced by L-Arg. Our results suggest that NO plays a role in the acquisition of the CTA induced by LiCl. Furthermore, the results suggest that the 5-HT1A receptor plays an important role in the CTA induced by MB and 7-NI, thus indicating a possible interaction between the 5-HT and NO systems.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Role of the area postrema in radiation-induced taste aversion learning and emesis in cats.

The role of the area postrema in radiation-induced emesis and taste aversion learning and the relationship between these behaviors were studied in cats. The potential involvement of neural factors which might be independent of the area postrema was minimized by using low levels of ionizing radiation (100 rads at a dose rate of 40 rads/min) to elicit a taste aversion, and by using body-only exposures (4500 and 6000 rads at 450 rads/min) to produce emesis. Lesions of the area postrema disrupted both taste aversion learning and emesis following irradiation. These results, which indicate that the area postrema is involved in the mediation of both radiation-induced emesis and taste aversion learning in cats under these experimental conditions, are interpreted as being consistent with the hypotheses that similar mechanisms mediate both responses to exposure to ionizing radiation, and that the taste aversion learning paradigm can therefore serve as a model system for studying radiation-induced emesis.

Animals↗

Heritable variation in food preferences and their contribution to obesity.

What an animal chooses to eat can either induce or retard the development of obesity; this review summarizes what is known about the genetic determinants of nutrient selection and its impact on obesity in humans and rodents. The selection of macronutrients in the diet appears to be, in part, heritable. Genes that mediate the consumption of sweet-tasting carbohydrate sources have been mapped and are being isolated and characterized. Excessive dietary fat intake is strongly tied to obesity, and several studies suggest that a preference for fat and the resulting obesity are partially genetically determined. Identifying genes involved in the excess consumption of dietary fat will be an important key to our understanding of the genetic disposition toward common dietary obesity.

Animals↗