Cross-adaptation and molecular modeling study of receptor mechanisms common to four taste stimuli in humans

Psychophysical cross-adaptation experiments were performed with twocarbohydrates, sucrose (SUC) and fructose (FRU), and two sweeteners,acesulfame-K (MOD) and dulcin (DUL). Seven subjects were asked to matchconcentrations that elicited the same intensity as a sucrose reference (30g/l). Cross-adaptation levels were calculated as the ratio of isointenseconcentrations measured for a given stimulus before and under adaptation.On average, cross-adaptation between SUC and FRU is low and apparentlyreciprocal. By contrast, cross-adaptation between SUC and MOD is clearlynon-reciprocal: SUC adapts MOD significantly (24%, P < 0.005), but MODfails to adapt SUC (2%, P < 0.79). Significant and reciprocalcross-enhancement is observed between DUL and MOD (approximately -20%, P< 0.03), and also between SUC and DUL (approximately -15%, P < 0.08).In parallel, molecular modeling of the four tastants was performed in orderto look for the 12 common binding motifs that were isolated on 14 othertastants in a previous study. SUC and FRU each display 10 out of the 12binding motifs, whereas DUL and MOD only display four and five distinctmotifs respectively and do not have any motif in common. Experimentalcross-adaptation levels seem to correlate well with the number of motifsthat molecules have in common. FRU and SUC share a majority of bindingmotifs and correlatively show mutual cross-adaptation. Four motifs of MODare found among the 10 motifs of SUC, which may explain why SUCcross-adapts MOD but not vice versa. By contrast, DUL and MOD do not shareany motif and do not cross- adapt. The various molecular mechanisms thatmay be responsible for cross-adaptation and/or cross-enhancement arediscussed in light of our results.