Calcium-sensing receptor mediates dietary peptide-induced CCK secretion in enteroendocrine STC-1 cells.
METHODS
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 (CaSR) mediates CCK secretion induced by amino acids. We investigated the role of CaSR 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.


RESULTS
CCK secretions in response to these hydrolysates were measured in the STC-1 cells with or without CaSR antagonist (NPS 2143) treatment. Changes in intracellular calcium concentration ([Ca²⁺](i) ) in response to protein hydrolysates were measured in Human embryonic kidney (HEK) 293 cells transfected with CaSR-expression vector. Protein hydrolysates-induced CCK secretions were decreased by CaSR antagonist treatment, except meat hydrolysate-induced secretion. Protein hydrolysates increased [Ca²⁺](i) in CaSR-transfected HEK 293 cells. CaSR 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 Da) derived from various protein hydrolysates were also reduced by CaSR antagonist.


CONCLUSIONS
These results demonstrate that CaSR plays a significant role in sensing various dietary peptides in triggering CCK secretion in enteroendocrine cells.
Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo, Japan.
Shingo
S
Nakajima
Tohru
T
Hira
Hiroshi
H
Hara
D000596:Amino Acids / Q000032:analysis / Q000494:pharmacology; D000818:Animals; D052179:Antigens, Plant / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002364:Caseins / Q000494:pharmacology; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000378:metabolism*; D004044:Dietary Proteins / Q000494:pharmacology*; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism*; D005916:Globulins / Q000494:pharmacology; D006801:Humans; D008460:Meat; D051379:Mice; D008970:Molecular Weight; D010446:Peptide Fragments / Q000494:pharmacology; D000074011:Peptide Transporter 1; D011492:Protein Hydrolysates / Q000494:pharmacology*; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D055314:Seed Storage Proteins / Q000494:pharmacology; D011198:Solanum tuberosum / Q000737:chemistry; D030262:Soybean Proteins / Q000494:pharmacology; D027981:Symporters / Q000037:antagonists & inhibitors; D062366:para-Aminobenzoates / Q000494:pharmacology
D000596:Amino Acids; D052179:Antigens, Plant; C095550:CASR protein, human; D002364:Caseins; D004044:Dietary Proteins; D005916:Globulins; D010446:Peptide Fragments; D000074011:Peptide Transporter 1; D011492:Protein Hydrolysates; D044169:Receptors, Calcium-Sensing; D055314:Seed Storage Proteins; D030262:Soybean Proteins; D027981:Symporters; C013894:beta-conglycinin protein, Glycine max; D062366:para-Aminobenzoates; C015668:4-aminomethylbenzoic acid; D002766:Cholecystokinin; D002118:Calcium