TRPM5 is critical for linoleic acid-induced CCK secretion from the enteroendocrine cell line, STC-1.
TRPM5 is critical for linoleic acid-induced CCK secretion from the enteroendocrine cell line, STC-1.
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DOI：
10.1152/ajpcell.00209.2011
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
B. Shah;Pin Liu;Tian Yu;D. R. Hansen;T. Gilbertson
中科院分区：
文献类型：
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作者：
B. Shah;Pin Liu;Tian Yu;D. R. Hansen;T. Gilbertson
脂肪酸诱导的肠内分泌细胞的刺激导致激素的释放，如胆囊收缩素（CCK），有助于饱腹感。最近，脂肪酸激活的G蛋白偶联受体GPR 120已被证明介导长链不饱和游离脂肪酸诱导的肠内分泌细胞系STC-1释放CCK，但下游信号通路仍不清楚。在这里，我们表明，亚油酸（LA）eleventh膜去极化和细胞内钙上升STC-1细胞，这些反应显着减少时，G蛋白或磷脂酶C的活性被阻断。LA导致STC-1细胞中单价阳离子特异性瞬时受体电位通道类型M5（TRPM 5）的激活。当使用RNA干扰降低TRPM 5或GPR 120的表达时，LA诱导的TRPM 5电流显著降低。此外，当使用RNA干扰降低TRPM 5通道的表达时，LA诱导的细胞内钙和CCK分泌的升高大大减少，这与TRPM 5在STC-1细胞中LA诱导的CCK分泌中的作用一致。
Fatty acid-induced stimulation of enteroendocrine cells leads to release of the hormones such as cholecystokinin (CCK) that contribute to satiety. Recently, the fatty acid activated G protein-coupled receptor GPR120 has been shown to mediate long-chain unsaturated free fatty acid-induced CCK release from the enteroendocrine cell line, STC-1, yet the downstream signaling pathway remains unclear. Here we show that linoleic acid (LA) elicits membrane depolarization and an intracellular calcium rise in STC-1 cells and that these responses are significantly reduced when activity of G proteins or phospholipase C is blocked. LA leads to activation of monovalent cation-specific transient receptor potential channel type M5 (TRPM5) in STC-1 cells. LA-induced TRPM5 currents are significantly reduced when expression of TRPM5 or GPR120 is reduced using RNA interference. Furthermore, the LA-induced rise in intracellular calcium and CCK secretion is greatly diminished when expression of TRPM5 channels is reduced using RNA interference, consistent with a role of TRPM5 in LA-induced CCK secretion in STC-1 cells.