Fatty acid‐induced cholecystokinin secretion and changes in intracellular Ca2+ in two enteroendocrine cell lines, STC‐1 and GLUTag

作者：Sukhvinder Sidhu, David G. Thompson, G. Warhurst, R. M. Case∥, Rod Benson · 发表于：The Journal of Physiology · 年份：2000 · DOI：10.1111/j.1469-7793.2000.00165.x · 被引用次数：87 · 研究领域：Neuropeptides and Animal Physiology、Biochemical Analysis and Sensing Techniques、Immune Response and Inflammation

1. Fatty acid-induced cholecystokinin (CCK) secretion in humans and from the enteroendocrine cell line STC-1 depends critically on acyl chain length. 2. Therefore we have characterized the relationship between acyl chain length and the potency of the fatty acid to induce CCK secretion and changes in intracellular Ca2+ concentration ([Ca2+]i) in two enteroendocrine cell lines (STC-1 and GLUTag). We found that the potency of the fatty acid was directly proportional to its chain length and therefore inversely proportional to its solubility. 3. In both cell types, the fatty acid-induced rise in [Ca2+]i in response to decanoic acid (C10), dodecanoic acid (C12) and tetradecanoic acid (C14) was significantly reduced in Ca2+-free medium and largely blocked by nicardipine. Intracellular stores also contributed to the overall shape of the [Ca2+]i peak. Thus all the fatty acids tested caused the release of Ca2+ from stores and influx of extracellular Ca2+, presumably through L-type calcium channels. 4. To probe the site of fatty acid action, we studied the distribution of 14C-labelled dodecanoic acid. This label was rapidly and irreversibly accumulated by both cell types, where it became concentrated about 20-fold. Confocal microscopy of a fluorescent analogue of dodecanoic acid clearly demonstrated that it entered the cytosol and was not merely partitioning in the cell membrane. These data indicate that an intracellular action for fatty acid-induced CCK secretion cannot be eliminated. ...