Platelet-activating factor contributes to immune cell and oxidant- mediated intestinal secretion

Thomas A. Hinterleitner, John D. Valentich, Jih Ho Cha, Peter Will, Ann Welton, Don W. Powell

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Abstract

The sensitivity of the Ussing-chambered rat colon to stimulation of Cl- secretion (as measured by the change in short-circuit current) by exogenous platelet-activating factor (PAF) was increased significantly by washing the colon in vitro with Ringer's solution containing fatty acid-free albumin. When the wash solution was extracted with chloroform/methanol and the lipid extract was added back to Ussing-chambered colons, inhibition of PAF- stimulated short-circuit current was observed, whereas short-circuit current responses to bradykinin or vasoactive intestinal peptide were not affected. Hypoxia appears to be an important trigger for the down-regulation of the PAF response. These data suggest that hypoxia releases PAF or an endogenous lipid PAF inhibitor that desensitizes PAF receptors on colonic epithelial or mucosal cells. The short-circuit current response of rabbit colon to the chemotactic peptide formyl-methionyl-leucyl-phenylalanine was not inhibited by any PAF antagonist devoid of cyclooxygenase inhibitory activity but was strongly inhibited by indomethacin. In contrast, anti-IgE- or H2O2- stimulated short-circuit current in rat colon was inhibited by specific PAF antagonists, and this inhibition was additive with indomethacin. Both anti- IgE and H2O2 significantly increased PAF production by rat colon. These data suggest that PAF plays an important role in oxidant (H2O2)- and anti- IgE-mediated colonic Cl- secretion but not in Cl- secretion mediated by formyl-methionyl-leucyl-phenylalanine-stimulated phagocytes.

Original languageEnglish (US)
Pages (from-to)1264-1271
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume281
Issue number3
StatePublished - Jun 1 1997

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Hinterleitner, T. A., Valentich, J. D., Cha, J. H., Will, P., Welton, A., & Powell, D. W. (1997). Platelet-activating factor contributes to immune cell and oxidant- mediated intestinal secretion. Journal of Pharmacology and Experimental Therapeutics, 281(3), 1264-1271.