Platelet-Activating Factor Contributes to Immune Cell and Oxidant-Mediated Intestinal Secretion

• Published in: The Journal of pharmacology and experimental therapeutics 1997-06, Vol.281 (3), p.1264
• Main Authors: Hinterleitner, T A, Valentich, J D, Cha, J H, Will, P, Welton, A, Powell, D W
• Format: Article
• Language: English
• Subjects: Animals; Chlorides - metabolism; Colon - drug effects; Colon - secretion; Dose-Response Relationship, Drug; Male; Oxidants - pharmacology; Platelet Activating Factor - pharmacology; Rats; Rats, Sprague-Dawley
• ISSN: 0022-3565; 1521-0103

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 H 2 O 2 -stimulated short-circuit current in rat colon was inhibited by specific PAF antagonists, and this inhibition was additive with indomethacin. Both anti-IgE and H 2 O 2 significantly increased PAF production by rat colon. These data suggest that PAF plays an important role in oxidant (H 2 O 2 )- and anti-IgE-mediated colonic Cl − secretion but not in Cl − secretion mediated by formyl-methionyl-leucyl-phenylalanine-stimulated phagocytes.