Synergistic Effect of Kokumi-Active γ-Glutamyl Peptides and l-Glutamate on Enhancing Umami Sensation and Stimulating Cholecystokinin Secretion via T1R1/T1R3 Activation in STC-1 Cells

This study aimed to investigate the synergistic effect of γ-glutamyl peptides (γEL, γEV, and γEγEV) and l-glutamate (MSG) on the activation of the umami receptor (T1R1/T1R3) in relation to enhanced umami taste and promoted cholecystokinin (CCK) secretion. The synergy of γ-glutamyl peptides and MSG (1-15 mM, 1:1) caused a significant increase in both the umami taste score by 0.218 ± 0.015-1.216 ± 0.031 times and the CCK secretion by 41.41 ± 6.46-201.16 ± 12.91% when compared to the group treated with individual MSG. The increase in CCK secretion promoted by γ-glutamyl peptides was only reduced by 11.54 ± 0.01-45.65 ± 3.58% after adding yjr CaSR inhibitor (NPS 2143), implying that there were other receptors besides CaSR involved in the stimulation of CCK secretion. The mixture of γEγEV and MSG synergistically increased the intracellular calcium release by 111.26 ± 11.94-135.28 ± 16.60% in STC-1 and 108.47 ± 7.89-152.33 ± 26.26% in HEK 293 compared to MSG. The protein expression for T1R1/T1R3 was increased, indicating that the mixture can activate T1R1/T1R3. The amino acids V277, S147, and D190 of T1R3 can be critical for the binding of γEγEV to T1R3. This is the first report on the synergistic effect of taste-active substances on taste sensation and hormone release via taste receptor activation.