Calcium‐sensing receptor mediates dietary peptide‐induced CCK secretion in enteroendocrine STC‐1 cells

Scope Dietary peptides are potent stimulators of cholecystokinin ( CCK ) secretion, but the sensing mechanism in CCK ‐producing cells is poorly understood. Recently, it has been demonstrated that the calcium‐sensing receptor ( C a SR ) mediates CCK secretion induced by amino acids. We investigated the role of C a SR in CCK secretions induced by various protein hydrolysates (egg albumin, meat, casein, azuki bean, soybean ß ‐conglycinin, and potato) in the enteroendocrine cell line STC ‐1. Methods and results CCK secretions in response to these hydrolysates were measured in the STC ‐1 cells with or without C a SR antagonist ( NPS 2143) treatment. Changes in intracellular calcium concentration ([ C a 2+ ] i ) in response to protein hydrolysates were measured in Human embryonic kidney (HEK) 293 cells transfected with C a SR ‐expression vector. Protein hydrolysates‐induced CCK secretions were decreased by C a SR antagonist treatment, except meat hydrolysate‐induced secretion. Protein hydrolysates increased [ C a 2+ ] i in C a SR ‐transfected HEK 293 cells. C a SR antagonist treatment suppressed low molecular weight fractions of azuki hydrolysate‐induced CCK secretion, but the secretion induced by both low and high molecular weight fractions of ß ‐conglycinin hydrolysate. Further, CCK secretion induced by peptide fractions (>500 D a) derived from various protein hydrolysates were also reduced by C a SR antagonist. Conclusion These results demonstrate that C a SR plays a significant role in sensing various dietary peptides in triggering CCK secretion in enteroendocrine cells.