Abstract |
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.
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Authors | R J MacLeod, P Lembessis, J R Hamilton, W S Powell |
Journal | The Journal of pharmacology and experimental therapeutics
(J Pharmacol Exp Ther)
Vol. 291
Issue 2
Pg. 511-6
(Nov 1999)
ISSN: 0022-3565 [Print] United States |
PMID | 10525065
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chloride Channels
- Leukotrienes
- Potassium Channel Blockers
- Vasoactive Intestinal Peptide
- Protein Kinase C
- 8,11,14-Eicosatrienoic Acid
- Bradykinin
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Topics |
- 8,11,14-Eicosatrienoic Acid
(pharmacology)
- Animals
- Bradykinin
(pharmacology)
- Chloride Channels
(antagonists & inhibitors)
- Dose-Response Relationship, Drug
- Guinea Pigs
- Intestinal Mucosa
(drug effects)
- Jejunum
(drug effects)
- Leukotrienes
(pharmacology)
- Male
- Potassium Channel Blockers
- Protein Kinase C
(antagonists & inhibitors)
- Time Factors
- Vasoactive Intestinal Peptide
(pharmacology)
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