BACKGROUND It is known that cholecystokinin (CCK) plays an essential role in reducing food intake and driving weight loss. Previous studies demonstrated that amino acids were capable of triggering CCK release through G protein-coupled receptors, but the sensing mechanism remains obscure, especially the intracellular signaling pathway. RESULTS L-Glu rather than its D-isomer robustly stimulated CCK secretion in a porcine duodenal model, and the secretory response was augmented by incubation with the allosteric ligand of T1R1, while T1R3 antagonist attenuated it. Upon inhibiting phospholipase C (PLC) or transient receptor potential M5 (TRPM5) activity, L-Glu failed to increase CCK release. Additionally, oral administration of monosodium glutamate in rats suppressed food intake and increased plasma CCK levels, accompanied with the elevated expression of T1R1, PLCβ2 and TRPM5 in the duodenum. CONCLUSION These data demonstrated that L-Glu stimulated CCK secretion through the activation of T1R1/T1R3 in a PLC/TRPM5-dependent manner. This article is protected by copyright. All rights reserved.

中文翻译：

---

L-谷氨酸通过 T1R1/T1R3 介导的 PLC/TRPM5 转导通路刺激胆囊收缩素分泌

背景众所周知，胆囊收缩素（CCK）在减少食物摄入和推动体重减轻方面起着至关重要的作用。先前的研究表明，氨基酸能够通过 G 蛋白偶联受体触发 CCK 释放，但其传感机制仍不清楚，尤其是细胞内信号通路。结果 L-Glu 而不是其 D-异构体在猪十二指肠模型中强烈刺激 CCK 分泌，分泌反应通过与 T1R1 的变构配体孵育而增强，而 T1R3 拮抗剂则减弱它。在抑制磷脂酶 C (PLC) 或瞬时受体电位 M5 (TRPM5) 活性后，L-Glu 未能增加 CCK 释放。此外，大鼠口服谷氨酸钠可抑制食物摄入并增加血浆 CCK 水平，伴随着十二指肠中 T1R1、PLCβ2 和 TRPM5 的表达升高。结论 这些数据表明，L-Glu 以 PLC/TRPM5 依赖性方式通过激活 T1R1/T1R3 刺激 CCK 分泌。本文受版权保护。版权所有。