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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 1997

Fingerprint

Intestinal Secretions
Platelet Activating Factor
Oxidants
Colon
methionyl-leucyl-phenylalanine
Indomethacin
Lipids
Vasoactive Intestinal Peptide
Bradykinin
Prostaglandin-Endoperoxide Synthases
Phagocytes
Chloroform
Nonesterified Fatty Acids
Methanol
Albumins
Down-Regulation
Rabbits
Peptides

ASJC Scopus subject areas

  • 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.

Platelet-activating factor contributes to immune cell and oxidant- mediated intestinal secretion. / Hinterleitner, Thomas A.; Valentich, John D.; Cha, Jih Ho; Will, Peter; Welton, Ann; Powell, Don W.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 281, No. 3, 06.1997, p. 1264-1271.

Research output: Contribution to journalArticle

Hinterleitner, TA, Valentich, JD, Cha, JH, Will, P, Welton, A & Powell, DW 1997, 'Platelet-activating factor contributes to immune cell and oxidant- mediated intestinal secretion', Journal of Pharmacology and Experimental Therapeutics, vol. 281, no. 3, pp. 1264-1271.
Hinterleitner, Thomas A. ; Valentich, John D. ; Cha, Jih Ho ; Will, Peter ; Welton, Ann ; Powell, Don W. / Platelet-activating factor contributes to immune cell and oxidant- mediated intestinal secretion. In: Journal of Pharmacology and Experimental Therapeutics. 1997 ; Vol. 281, No. 3. pp. 1264-1271.
@article{46af8c59aacb4dc9b4cb3523d7f66bfd,
title = "Platelet-activating factor contributes to immune cell and oxidant- mediated intestinal secretion",
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.",
author = "Hinterleitner, {Thomas A.} and Valentich, {John D.} and Cha, {Jih Ho} and Peter Will and Ann Welton and Powell, {Don W.}",
year = "1997",
month = "6",
language = "English (US)",
volume = "281",
pages = "1264--1271",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "3",

}

TY - JOUR

T1 - Platelet-activating factor contributes to immune cell and oxidant- mediated intestinal secretion

AU - Hinterleitner, Thomas A.

AU - Valentich, John D.

AU - Cha, Jih Ho

AU - Will, Peter

AU - Welton, Ann

AU - Powell, Don W.

PY - 1997/6

Y1 - 1997/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0030953666&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030953666&partnerID=8YFLogxK

M3 - Article

VL - 281

SP - 1264

EP - 1271

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 3

ER -