Investigation of the effects of platelet-activating factor (PAF) on ion transport and prostaglandin synthesis in human colonic mucosa in vitro.
1 We have investigated the effects of platelet-activating factor (PAF), an endogenous mediator of inflammation, on ion transport and prostaglandin synthesis in the human isolated colon. 2 Application of PAF to the serosal surface of human colonic mucosa induced a marked, concentration-dependent increase in ion transport. Mucosal application was without effect. 3 The secretory response to PAF was significantly inhibited by prior application of a specific PAF receptor antagonist WEB 2170, indicating that the response is dependent on PAF receptor activation. 4 The response to PAF was attenuated by prior application of indomethacin or piroxicam, implicating products of the cyclo-oxygenase pathway in the response. 5 The response to PAF was attenuated by the loop diuretic bumetanide, indicating an involvement of chloride ion secretion in the response. 6 Addition of PAF to the serosal surface induced a significant increase in serosal prostaglandin E2 (PGE2), but not 6-oxo-PGF1alpha release. There was no effect on mucosal application of PAF. 7 In summary, we have shown that PAF is a potent secretagogue in isolated preparations of human colon and that the response is dependent on a specific PAF receptor, cyclo-oxygenase products and bumetanide-sensitive chloride ion transport.
Borman
R A
RA
Clinical Pharmacology Group, School of Medicine, University of Southampton.
Jewell
R
R
Hillier
K
K
D001381:Azepines / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D003106:Colon / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism*; D007477:Ions; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011453:Prostaglandins / Q000096:biosynthesis*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D007477:Ions; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011453:Prostaglandins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C063964:bepafant