CROSS-ADAPTATION AND MOLECULAR MODELING STUDY OF RECEPTOR MECHANISMS COMMON TO 4 TASTE STIMULI IN HUMANS

Psychophysical cross-adaptation experiments were performed with two ca rbohydrates, sucrose (SUC) and fructose (FRU), and two sweeteners, ace sulfame-K (MOD) and dulcin (DUL):. Seven subjects were asked to match concentrations that elicited the same intensity as a sucrose reference (30 g/l). Cross-adaptation levels were calculated as the ratio of iso intense concentrations measured for a given stimulus before and under adaptation. On average, cross-adaptation between SUC and FRU is low an d apparently reciprocal. By contrast, cross-adaptation between SUC and MOD is clearly non-reciprocal: SUC adapts MOD significantly (24%, P < 0.005), but MOD fails to adapt SUC (2%, P < 0.79). Significant and re ciprocal cross-enhancement is observed between DUL and MOD (similar to -20%, P < 0.03), and also between SUC and DUL (similar to-15%, P < 0.0 8). In parallel, molecular modeling of the four tastants was performed in order to look for the 12 common binding motifs that were isolated on 14 other tastants in a previous study. SUC and FRU each display 10 out of the 12 binding motifs, whereas DUL and MOD only display four an d five distinct motifs respectively and do not have any motif in commo n. Experimental cross-adaptation levels seem to correlate well with th e number of motifs that molecules have in common. FRU and SUC share a majority of binding motifs and correlatively show mutual cross-adaptat ion. Four motifs of MOD are found among the 10 motifs of SUC, which ma y explain why SUC cross-adapts MOD but not vice versa. By contrast, DU L and MOD do not share any motif and do not cross-adapt. The various m olecular mechanisms that may be responsible for cross-adaptation and/o r cross-enhancement are discussed in light of our results.