Evidence Supporting Multiple Receptor-Transduction Mechanism

Chapter 6

Clustering Bitter Compounds via Individual Sensitivity Differences: Evidence Supporting Multiple Receptor-Transduction Mechanisms 1,2

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Downloaded by FUDAN UNIV on January 5, 2017 | http://pubs.acs.org Publication Date: July 19, 2002 | doi: 10.1021/bk-2002-0825.ch006

Jeannine F. Delwiche , Zivjena Buletic , and Paul A. S. Breslin 1

Department of Food Science and Technology, Ohio State University, 2015 Fyffe Road, Columbus, OH 43210 2

Monell Chemical Senses Center, 3500 Market Street, Philadelphia, P A 19104

Although it had been well documented that people varied widely in their sensitivities to bitter compounds, the intercorrelation of these sensitivities remained unknown. By clustering bitter compounds representative of different chemical classes as a function of individual sensitivities, it was possible to infer the number and variety of potential bitterness transduction systems involved in bitter perception. Results indicated that bitter compounds could be grouped into two general groups, neither of which contains PROP (n-propylthiouracil). There are also subjects who possess diminished absolute sensitivity to bitter stimuli, but do not differ in their relative sensitivities to these compounds.

Compounds that elicit bitter-taste sensations are chemically diverse, and include both inorganic and organic compounds (1, 2). Compounds with bitter tastes have been categorized as acetylated sugars, alkaloids, amines, amino acids, carbamates, ionic salts, isohumulones, ureas/thioureas, phenols, etc. (1, 2). It is unlikely that a single bitter receptor can account for sensitivity to all

© 2002 American Chemical Society Given and Paredes; Chemistry of Taste ACS Symposium Series; American Chemical Society: Washington, DC, 2002.

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classes of compounds that are perceived to be bitter tasting (1, 3). The possibility that classes of bitter transduction processes in the general population could be revealed by examining and correlating individual differences in sensitivities to bitter compounds was recently examined by Delwiche et al. (4). Their approach was motivated by the observation that large individual differences in the bitterness of a variety of compounds have been reported. The most frequently studied variation among subjects' sensitivities to bitter chemicals has been for PROP (n-propylthiouracil), PTC (phenylthiocarbamide) and other antithyroid compounds that contain the N-C=S chemical group, (e.g., 5-12), although wide-ranging responses across individuals to other bitter compounds have been found as well (7). Despite numerous attempts to relate how strongly one perceives a particular concentration of PROP/PTC to how strongly one perceives particular concentrations of other bitter substances (including quinine, caffeine and urea), PROP/PTC has not proven to be a reliable indicator (7, 9, 13-17). Nevertheless, the possibility remains that individuals' sensitivities to other bitter compounds will correlate with each other. The existence of more than one physiological transduction mechanism in the perception of bitterness is suggested by the substantial variation in sensitivities to different bitter-tasting compounds. V i a primary neural recordings, Dahl et al. (18) attempted to infer the idiosyncratic distribution of transduction mechanisms for bitter taste stimuli in rat taste-receptor cells. They recorded single neuron responses to 10 bitter-tasting compounds in rats and summarized differences in evoked responses in multi-dimensional scaling space. The majority of physiological papers have only focused upon a small subset of bitter compounds, and many have used only a single compound - usually quinine (as noted by Dahl et al. in Ref 18). Similarly, many psychophysical studies have limited themselves to one or a few of the following bitter-tasting compounds: quinine, caffeine, urea, PTC, and PROP (e.g., 9, 10, 15, 17). The use of so few stimuli makes it difficult, i f not impossible, to find covariance in perceived intensities across compounds. It may be possible to infer the number and variety of potential bitterness transduction systems for the compounds tested by adapting a strategy similar to that of Dahl et al. (18) and determining i f compounds cluster together in humans as a function of sensitivities across individuals. Applying a related approach, Yokomukai et al. (7) found that sensitivity to quinine sulfate and urea were unrelated, but individuals more sensitive to quinine than urea tended to find the bitterness of suprathreshold caffeine and sucrose octaacetate (SOA) to be greater than that of suprathreshold magnesium sulfate; individuals more sensitive to urea than quinine showed the reverse pattern. McBurney et al. (19) found that adaptation to quinine hydrochloride significantly decreased the perceived bitterness of S O A and caffeine, but not

Given and Paredes; Chemistry of Taste ACS Symposium Series; American Chemical Society: Washington, DC, 2002.

67 magnesium sulfate, while adaptation to urea significantly decreased the perceived bitterness of magnesium sulfate, but not SOA and caffeine. Similarly, Lawless (14) confirmed these findings for quinine, urea, and creatine.


Idiosyncratic Patterns of Perceived Bitter Intensity In a recent extensive study by Delwiche et al. (4), the perceived intensities of bitter-tasting compounds reported by 26 individuals were examined for evidence of covariation in perceived bitter intensity. The subjects rated the bitter intensity of 11 chemically diverse compounds (typically described as bitter) using the L M S scale (20, 21). These compounds, and their concentrations, were as follows: 1.19 χ 10' M quinine hydrochloride, 5.70 χ 10" M sucrose octaacetate, 9.20 χ 10 M urea, 1.37 χ 10" M tetralone® (a mixture of iso-alpha-acids), 5.02 χ 10" M L-phenylalanine, 2.69 χ 10" M L-tryptophan, 1.09 χ 10' M caffeine, 3.00 χ 10" M magnesium sulfate, 4.99 χ 10" M denatonium benzoate, 1.72 χ 10" M (-)-epicatechin and 5.50 χ ΙΟ^Μ n-propylthiouracil (PROP). In addition, these same subjects repeatedly ranked a subset of 9 of these compounds (all but epicatechin and PROP, due to expense and context effects, respectively) from weakest to strongest in bitterness, and a significant ranked order was determined for each individual (for more details on the psychophysical methodology, see Ref 4). Pearson's product moment correlation coefficients were calculated for the rated intensities of all 11 compounds and Spearman's rho correlation coefficients were calculated for the bitter ranks of the 9 ranked compounds (see Table 1). Only three compound-pairs showed significant correlations in both data sets: caffeine/SOA, caffeine/tetralone®, and phenylalanine/tryptophan. No significant correlation was found between PROP and the ten remaining compounds for rated intensities (p>0.05, post-Bonferroni correction). This is especially striking since every other compound correlated significantly with at least one other compound, and the bitterness ratings of S O A correlated significantly with those of four other compounds (see Table 1, bottom). Similarly, with the ranked data, several significant correlations were found (see Table 1, top), but unlike with rated intensities, over half of the significant correlations were negative. However, it is important to note that every significant negative correlation found for the ranking data was a nonsignificant correlation for the ratings. The apparent discrepancies between the correlations based on ratings and those based on rankings can be explained by the fact that the ranking methodology is insensitive to absolute differences between subjects in perceived intensities, which allow negative correlations to be revealed. In contrast, with rating procedures some subjects consistently give higher ratings, 4

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Given and Paredes; Chemistry of Taste ACS Symposium Series; American Chemical Society: Washington, DC, 2002.

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and others lower ratings, to all bitter compounds, leading to positive correlations across subjects. A s a consequence, negative correlations in the ranking data appeared as weakly positive correlations in the rating data.

NOTE: Pearson's product moment correlation coefficients of bitter ratings (unshaded cells) and Spearman's Rho correlation coefficients of bitter ranking (shaded cells). Correlations in bold are significant at p

Evidence Supporting Multiple Receptor-Transduction Mechanism

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