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 (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.
Footnotes
-
Send reprint requests to: Dr. William S. Powell, Meakins-Christie Laboratories, McGill University, 3626 St. Urbain St., Montreal, Quebec, Canada H2X 2P2. E-mail: bill{at}meakins.lan.mcgill.ca
-
↵1 This work was supported by grants from the Medical Research Council of Canada (MT-6708 to J.R.H. and MT-6254 to W.S.P.).
-
↵2 Present address: Endocrine-Hypertension Division, Department of Medicine, Brigham and Women’s Hospital, 221 Longwood Ave., Boston, MA 02115-5817.
- Abbreviations:
- LT
- leukotriene
- LTB4
- leukotriene B4
- 5-oxo-ETE
- 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid
- 5-HETE
- 5(S)-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid
- VIP
- vasoactive intestinal peptide
- PKC
- protein kinase C
- 8-Br
- 8-bromoadenosine
- A-9C
- anthracene-9-carboxylate
- IAA-94
- indanyloxyacetic acid 94
- Received April 13, 1999.
- Accepted July 14, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|