PT  - JOURNAL ARTICLE
AU  - MacLeod, R. John
AU  - Lembessis, P.
AU  - Hamilton, J. R.
AU  - Powell, William S.
TI  - 5-Oxo-6,8,11,14-eicosatetraenoic Acid Stimulates Isotonic Volume Reduction of Guinea Pig Jejunal Crypt Epithelial Cells
DP  - 1999 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 511--516
VI  - 291
IP  - 2
4099  - http://jpet.aspetjournals.org/content/291/2/511.short
4100  - http://jpet.aspetjournals.org/content/291/2/511.full
SO  - J Pharmacol Exp Ther1999 Nov 01; 291
AB  - 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 (EC50 = 20 pM) was more potent than any of the other agonists tested, including its precursor, 5-hydroxy-6,8,11,14-eicosatetraenoic acid (EC50 = 5 nM); leukotriene D4 (EC50 = 1 nM); vasoactive intestinal peptide (EC50 = 200 pM); and bradykinin (EC50 = 50 nM). Leukotriene B4had 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. The American Society for Pharmacology and Experimental Therapeutics