MacLeod R J, Lembessis P, Hamilton J R, Powell W S
Department of Pediatrics, McGill University, Montreal Children's Hospital, Montreal, Quebec, Canada.
J Pharmacol Exp Ther. 1999 Nov;291(2):511-6.
5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a recently discovered arachidonate metabolite that is a potent activator of eosinophils and neutrophils and may be an important mediator of inflammation. The objective of the present investigation was to determine whether 5-oxo-ETE affects the isotonic volume of Cl(-) secretory intestinal crypt epithelial cells. 5-Oxo-ETE caused rapid shrinkage of guinea pig jejunal crypt epithelial cells to a reduced but stable volume, which was measured electronically. This effect was prevented by Cl(-) and K(+) channel blockers and inhibitors of protein kinase C. 5-Oxo-ETE (EC(50) = 20 pM) was more potent than any of the other agonists tested, including its precursor, 5-hydroxy-6,8,11,14-eicosatetraenoic acid (EC(50) = 5 nM); leukotriene D(4) (EC(50) = 1 nM); vasoactive intestinal peptide (EC(50) = 200 pM); and bradykinin (EC(50) = 50 nM). Leukotriene B(4) had no effect on crypt cell volume. In contrast to its effects on crypt cells, 5-oxo-ETE had no effect on the volume of jejunal villus cells. These results indicate that 5-oxo-ETE induces an isotonic volume reduction in intestinal crypt epithelial cells that appears to be dependent on Cl(-) secretion and activation of protein kinase C.
5-氧代-6,8,11,14-二十碳四烯酸（5-氧代-ETE）是一种最近发现的花生四烯酸代谢产物，它是嗜酸性粒细胞和中性粒细胞的强效激活剂，可能是炎症的重要介质。本研究的目的是确定5-氧代-ETE是否影响氯离子分泌性肠隐窝上皮细胞的等渗体积。5-氧代-ETE导致豚鼠空肠隐窝上皮细胞迅速收缩至降低但稳定的体积，该体积通过电子方式测量。这种效应被氯离子和钾离子通道阻滞剂以及蛋白激酶C抑制剂所阻止。5-氧代-ETE（半数有效浓度（EC50）=20皮摩尔）比所测试的任何其他激动剂都更有效，包括其前体5-羟基-6,8,11,14-二十碳四烯酸（EC50 = 5纳摩尔）；白三烯D4（EC50 = 1纳摩尔）；血管活性肠肽（EC50 = 200皮摩尔）；以及缓激肽（EC50 = 50纳摩尔）。白三烯B4对隐窝细胞体积没有影响。与它对隐窝细胞的作用相反，5-氧代-ETE对空肠绒毛细胞的体积没有影响。这些结果表明，5-氧代-ETE诱导肠隐窝上皮细胞等渗体积减少，这似乎依赖于氯离子分泌和蛋白激酶C的激活。
