Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo, Japan.
Mol Nutr Food Res. 2012 May;56(5):753-60. doi: 10.1002/mnfr.201100666.
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.
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⁺ ) 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⁺ 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.
These results demonstrate that CaSR plays a significant role in sensing various dietary peptides in triggering CCK secretion in enteroendocrine cells.
膳食肽是强烈的胆囊收缩素 (CCK) 分泌刺激物，但在产生 CCK 的细胞中，其感应机制仍知之甚少。最近，已经证明钙敏感受体 (CaSR) 介导了氨基酸诱导的 CCK 分泌。我们研究了 CaSR 在各种蛋白水解物（卵白蛋白、肉、酪蛋白、红豆、大豆 β-伴球蛋白和土豆）诱导的 STC-1 肠内分泌细胞系 CCK 分泌中的作用。
在存在或不存在 CaSR 拮抗剂（NPS 2143）处理的情况下，用 STC-1 细胞测量对这些水解物的 CCK 分泌。用 CaSR 表达载体转染的人胚肾 (HEK) 293 细胞中测量了对蛋白水解物的细胞内钙离子浓度 (Ca²⁺) 的变化。除了肉水解物诱导的分泌外，CaSR 拮抗剂处理降低了蛋白水解物诱导的 CCK 分泌。蛋白水解物增加了 CaSR 转染的 HEK 293 细胞中的 Ca²⁺。CaSR 拮抗剂处理抑制了红豆水解物低分子量部分诱导的 CCK 分泌，但抑制了 β-伴球蛋白低分子量和高分子量部分诱导的 CCK 分泌。此外，各种蛋白水解物衍生的肽（>500 Da）诱导的 CCK 分泌也被 CaSR 拮抗剂减少。
这些结果表明 CaSR 在感应各种膳食肽触发肠内分泌细胞中 CCK 分泌方面起着重要作用。
