Fatty acids stimulate cholecystokinin secretion via an acyl chain length-specific, Ca2+-dependent mechanism in the enteroendocrine cell line STC-1
Fatty acids stimulate cholecystokinin secretion via an acyl chain length-specific, Ca2+-dependent mechanism in the enteroendocrine cell line STC-1
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DOI：
10.1111/j.1469-7793.1998.011by.x
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发表时间：
1998-11-15
影响因子：
5.5
通讯作者：
Warhurst, G
中科院分区：
文献类型：
--
作者：
McLaughlin, JT;Lomax, RB;Warhurst, G
1.本研究使用STC-1（一种小鼠肠内分泌肿瘤细胞系）研究脂肪酸是否直接影响肠内分泌细胞的肽释放，STC-1先前显示释放胆囊收缩素（CCK）以响应其他生理刺激.脂肪酸引起的CCK分泌的链长度和剂量依赖性刺激。十二烷酸（C12）是最有效的，产生高达5倍的CCK分泌增加。少于10个碳原子的脂肪酸不会增加分泌。这些效应的链长依赖性与以前在人体内观察到的脂肪酸诱导的CCK分泌密切相关。酯化C12废除CCK分泌，表明一个自由的羧基在引发分泌的关键作用。相反，甲基末端的修饰对GIB诱导的分泌没有影响。不可代谢的C12类似物2-溴代十二烷酸同样有效。C12在STC-1细胞中引起细胞内钙水平的显著增加（200-300 nM），其被L-型Ca 2+通道拮抗剂尼卡地平消除。相反，C8产生更小和更短暂的Ca 2+反应。尼卡地平也能阻断C12诱导的CCK分泌.这些数据表明，脂肪酸可以直接与肠内分泌细胞相互作用，刺激CCK分泌通过增加细胞内钙离子介导的主要是L型钙通道。
1.The present study has investigated whether fatty acids directly influence peptide release from enteroendocrine cells using STC-1, a mouse intestinal endocrine tumour cell line, previously shown to release cholecystokinin (CCK) in response to other physiological stimuli.2. Fatty acids elicited a chain length- and dose-dependent stimulation of CCK secretion. Dodecanoic acid (C12) was most effective, producing up to a 5-fold increase in CCK secretion. Fatty acids with less than ten carbon atoms did not increase secretion. The chain length dependence of these effects mimics closely fatty acid-induced CCK secretion previously observed in humans in vivo.3. Esterification of C12 abolished CCK secretion, indicating a critical role for a free carboxyl group in eliciting secretion. In contrast, modification of the methyl terminus had no effect on GIB-induced secretion. The non-metabolizable C12 analogue 2-bromododecanoic acid was equally effective.4. C12 elicited a marked increase in intracellular calcium levels (200-300 nM) in STC-1 cells which was abolished by the L-type Ca2+ channel antagonist nicardipine. In contrast, C8 produced a smaller and more transient Ca2+ response. C12-induced CCK secretion was also blocked by nicardipine.5. These data suggest that fatty acids can interact directly with enteroendocrine cells to stimulate CCK secretion via increases in intracellular calcium mediated primarily by L-type Ca2+ channels.