Platelet activating factor is a potent colonic secretagogue with actions independent of specific PAF receptors.
Several candidate mediators of acute inflammation such as E-type prostaglandins, histamine and bradykinin are potent pro-diarrhoeal colonic secretagogues. They act to increase serosal to mucosal transport of chloride and passive water efflux. We investigated the effects of platelet activating factor (PAF) on muscle-stripped rat colon, measuring transepithelial potential difference (p.d.) and, under voltage clamp conditions, short circuit current (Isc). PAF induced dose-dependent increases in p.d. and Isc, with an approximate EC50 of 1.5 X 10(-10) M; similar concentrations of lyso-PAF had a much smaller but discernible effect. PAF and lyso-PAF both displayed 'sidedness' with serosal application effective and mucosal application ineffective. Inhibitor studies suggest that chloride is the principal ion carrier, but the specific PAF receptor antagonists kadsurenone, L652731, CV 3988 and WEB 2086 did not block the response. Unlike bradykinin, PAF did not cause the release of PGE2 into the serosal bathing fluid, and its action was not attenuated by the cyclo-oxygenase inhibitors piroxicam, mefenamic acid or flurbiprofen. We conclude that PAF has a powerful pro-diarrhoeal secretory action on colonic epithelium which is not mediated by the previously defined PAF receptor(s) and is independent of prostanoid generation.
Buckley
T L
TL
Department of Pharmacology, King's College, Strand, London, U.K.
Hoult
J R
JR
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone / Q000494:pharmacology; D004594:Electrophysiology; D005665:Furosemide / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D005665:Furosemide; D015232:Dinoprostone; D001920:Bradykinin; D002118:Calcium