Umami-Enhancing Effects of Kokumi Peptides Associated with CaSR-Related Cellular Responses in STC-1 Cells

Abstract CaSR has been recognized as a potential receptor involved in kokumi peptide perception. However, the molecular basis underlying kokumi-peptide-induced cellular responses remains insufficiently understood. Herein, CaSR-associated responses induced by kokumi peptides were investigated in STC-1 cells. Compared with MSG stimulation alone, MSG combined with γ-glutamyl peptides enhanced intracellular Ca2+ mobilization and CCK secretion, with response trends consistent with sensory evaluation. MSG+γEγEV elicited the strongest cellular response, increasing CCK secretion from 31.38 ± 3.18 pg/mL in the MSG group to 60.84 ± 4.45 pg/mL, while Ca2+ fluorescence intensity increased by 133.60% relative to MSG treatment alone (p < 0.05). Pretreatment with the CaSR antagonist NPS-2143 reduced MSG+γEγEV-induced Ca2+ mobilization and CCK secretion by 51.09 and 42.90%, respectively, supporting the involvement of CaSR in these cellular responses. Metabolomic and transcriptomic analyses revealed alterations in signaling-associated metabolites and pathways, including calcium signaling, MAPK signaling, PI3K-Akt signaling, cAMP signaling, phosphoinositide-related metabolism, and glycerophospholipid metabolism. These findings suggest that signaling responses associated with CaSR involvement in STC-1 cells share certain features with taste-related signal transduction processes. Collectively, the results provide insights into kokumi-peptide-induced cellular responses and their potential relevance to umami enhancement.