ROLE OF PLATELET-ACTIVATING-FACTOR IN CHINESE-HAMSTER OVARY CELL RESPONSES TO CHOLERA-TOXIN

Cholera toxin (CT)-induced intestinal secretion and Chinese hamster ov ary cell (CHO) elongation involves cyclic adenosine monophosphate and protein synthesis-dependent prostaglandin formation. We previously rep orted inhibition of CT-induced intestinal secretion and CHO elongation by platelet-activating factor (PAF) receptor antagonists and secretio n of PAF by human intestinal epithelial cells exposed to CT. Herein, w e show that PAF is involved-after cAMP and that PAF, like CT, mediates prostaglandin E-2 synthesis in CHO cells. CT-induced CHO elongation w as blocked by specific PAF receptor antagonists, BN52021 and SR27417. SR27417 blocked dibutyryl cAMP-induced CHO elongation, but did not alt er CHO elongation caused by PGE(2). Neither CT-stimulated cAMP accumul ation nor PGE(2) production was inhibited by SR27417. Both PGE(2) and PAF caused significant CHO elongation, but the latter did not stimulat e significant cAMP production. In addition, PAF, like CT and dibutyryl cAMP, stimulated significant PGE, production. Finally, the protein sy nthesis inhibitor cycloheximide, which completely blocks the effect of CT on prostaglandin synthesis, also blocked that of PAF, suggesting t hat PAF also mediates protein synthesis-dependent prostaglandin format ion. We conclude that PAF is involved in CHO cytoskeletal responses to CT after the accumulation of cAMP and, like CT, PAF stimulates protei n synthesis-dependent prostaglandin accumulation.