Platelet activating factor: release from colonic mucosa in patients with ulcerative colitis and its effect on colonic secretion.
Inflammatory mediators have been implicated in the pathophysiology of ulcerative colitis. They may stimulate intestinal secretion and contribute to the production of diarrhoea. Platelet activating factor (PAF) may be responsible for a high proportion of this secretory response. Biopsy specimens from inflamed and quiescent mucosa of patients with ulcerative colitis and normal human colonic mucosa were cultured or co-cultured. The release of PAF, prostaglandin E2, and leukotriene D4 into the culture medium was measured and the ability of this culture medium, from inflamed and normal tissues, to influence secretion in rat colonic mucosa was assessed. PAF was liberated by inflamed tissue. Its release from quiescent but not normal tissue was stimulated by medium in which inflamed mucosal biopsy tissues had been cultured and by exogenous bradykinin and 5-hydroxytryptamine, but not by histamine. PAF stimulated eicosanoid production. The rise in short circuit current produced in vitro by inflamed tissue culture medium was inhibited by the PAF receptor antagonist (CV 6209) (46%) (32.4 (2.9) v 17.5 (1.19) muA.cm-2, p < 0.005) and further by combined cyclooxygenase and lipoxygenase inhibition (indomethacin plus ICI 207968) (58%) (32.4 (2.9) v 13.6 (1.9) muA.cm-2, p < 0.005). Mepacrine and hydrocortisone attenuated considerably the electrical response evoked by medium from inflamed mucosa to a similar extent (32.4 (2.9) v 6.3 (1.2) v 5.1 (0.9) muA.cm-2, p < 0.001). These data suggest that PAF accounted for 46% of the culture medium secretory effect. Thus, any attempt to block its release in patients with ulcerative colitis may have only a partial effect on their symptoms.
Wardle
T D
TD
Epithelial Membrane Research Centre, University of Manchester, Hope Hospital, Salford.
Hall
L
L
Turnberg
L A
LA
D000328:Adult; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D018920:Coculture Techniques; D003093:Colitis, Ulcerative / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D017077:Culture Media, Conditioned; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004594:Electrophysiology; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009924:Organ Culture Techniques; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012701:Serotonin / Q000494:pharmacology
D065168:Bradykinin Receptor Antagonists; D017077:Culture Media, Conditioned; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D012701:Serotonin; D006632:Histamine; D015232:Dinoprostone; D001920:Bradykinin