dictyNews
Electronic Edition
Volume 42, number 1
January 8, 2016
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Abstracts
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Bitter tastant responses in the amoeba Dictyostelium correlate with
rat and human taste assays
Marco Cocorocchio1, Robert Ives2, David Clapham3, Paul L.R. Andrews4,
Robin S.B. Williams1
1 Centre of Biomedical Sciences, School of Biological Sciences,
Royal Holloway University of London, Egham, TW20 0EX, UK
2 RD Platform Technology & Science, GlaxoSmithKline, Hertfordshire,
SG1 2NY, UK
3 RD Platform Technology & Science, GlaxoSmithKline, Hertfordshire,
SG12 ODP, UK
4 Division of Biomedical Science, St George’s University of London,
SW17 0RE, UK
published in ALTEX
Treatment compliance is reduced when pharmaceutical compounds
have a bitter taste and this is particularly marked for paediatric
medications. Identification of bitter taste liability during drug
discovery utilises the rat in vivo brief access taste aversion (BATA)
test which apart from animal use is time consuming with limited
throughput. We investigated the suitability of using a simple, non-
animal model, the amoeba Dictyostelium discoideum to investigate
taste-related responses and particularly identification of compounds
with a bitter taste liability. The effect of taste-related compounds
on Dictyostelium behaviour following acute exposure (15 minutes) was
monitored. Dictyostelium did not respond to salty, sour, umami or
sweet tasting compounds, however, cells rapidly responded to bitter
tastants. Using time-lapse photography and computer-generated
quantification to monitor changes in cell membrane movement, we
developed an assay to assess the response of Dictyostelium to a wide
range of structurally diverse known bitter compounds and blinded
compounds. Dictyostelium showed varying responses to the bitter
tastants, with IC50 values providing a rank order of potency.
Comparison of Dictyostelium IC50 values to those observed in response
to a similar range of compounds in the rat in vivo brief access taste
aversion test showed a significant (p = 0.0172) positive correlation
between the two models, and additionally a similar response to that
provided by a human sensory panel assessment test. These experiments
demonstrate that Dictyostelium may provide a suitable model for early
prediction of bitterness for novel tastants and drugs. Interestingly,
a response to bitter tastants appears conserved from single-celled
amoebae to humans.
submitted by: Robin Williams [[log in to unmask]]
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[End dictyNews, volume 42, number 1]
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