Vol. 291, Issue 2, 511-516, November 1999

5-Oxo-6,8,11,14-eicosatetraenoic Acid Stimulates Isotonic Volume Reduction of Guinea Pig Jejunal Crypt Epithelial Cells¹

R. John MacLeod² , P. Lembessis, J. R. Hamilton and William S. Powell

Department of Pediatrics, McGill University, Montreal Children's Hospital, Montreal, Quebec, Canada (R.J.M., P.L., J.R.H.); and Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada (W.S.P.)

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 B₄ 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.