PLATELET-ACTIVATING-FACTOR CONTRIBUTES TO IMMUNE CELL AND OXIDANT-MEDIATED INTESTINAL SECRETION

The sensitivity of the Ussing-chambered rat colon to stimulation of Cl - secretion (as measured by the change in short-circuit current) by ex ogenous platelet-activating factor (PAF) was increased significantly b y washing the colon in vitro with Ringer's solution containing fatty a cid-free albumin. When the wash solution was extracted with chloroform /methanol and the lipid extract was added back to Ussing-chambered col ons, inhibition of PAF-stimulated short-circuit current was observed, whereas short-circuit current responses to bradykinin or vasoactive in testinal peptide were not affected. Hypoxia appears to be an important trigger for the down-regulation of the PAF response. These data sugge st that hypoxia releases PAF or an endogenous lipid PAF inhibitor that desensitizes PAF receptors on colonic epithelial or mucosal cells. Th e short-circuit current response of rabbit colon to the chemotactic pe ptide formylmethionyl-leucyl-phenylalanine was not inhibited by any PA F antagonist devoid of cyclooxygenase inhibitory activity but was stro ngly inhibited by indomethacin. In contrast, anti-lgE- or H2O2-stimula ted short-circuit current in rat colon was inhibited by specific PAF a ntagonists, and this inhibition was additive with indomethacin. Both a nti-IgE and H2O2 significantly increased PAF production by rat colon. These data suggest that PAF plays an important role in oxidant (H(2O)2 )- and anti-IgE-mediated colonic Cl- secretion but not in Cl- secretio n mediated by formyl-methionyl-leucyl-phenylalanine-stimulated phagocy tes.