ROLE OF PLATELET-ACTIVATING-FACTOR IN THE INTESTINAL EPITHELIAL SECRETORY AND CHINESE-HAMSTER OVARY CELL CYTOSKELETAL RESPONSES TO CHOLERA-TOXIN

With the recent heightened concern about cholera around the world come new questions about the mechanism by which cholera toxin causes diarr hea. Peterson and Ochoa have suggested that prostaglandin synthesis is key to both the intestinal epithelial secretory and the CHO cell resp onses to cholera toxin [Peterson, J. W. and Ochoa, G. (1989) Science 2 45, 857-859]. Because platelet activating factor (PAF) can be a potent stimulus for prostaglandin synthesis, we examined its role in the int estinal and tissue culture effects of cholera toxin. We report that th e specific PAF receptor antagonists BN 52021 and SR 27417 inhibit the effects of cholera toxin on intestinal secretion in rabbit heal loops in vivo and on the cytoskeleton of Chinese hamster ovary cells in vitr o. We also show that PAF itself can cause net fluid secretion in the r abbit model and that PAF potentiates the effects of cholera toxin on i ntestinal secretion. Finally, we demonstrate that cholera toxin stimul ates significant PAF production (2.6-fold) in isolated T-84 intestinal epithelial cells. We conclude that cholera toxin stimulates PAF produ ction and that PAF is involved in both the secretory and cytoskeletal responses to cholera toxin. These findings further support the involve ment of additional mediators of cholera toxin effects other than mucos al cell cyclic AMP and help explain the effects of cholera toxin on pr ostaglandin synthesis.