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 E-2 (PGE(2)), but not 6-oxo-PGF(1 alpha) 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.