PAF effects on transmembrane signaling pathways in rat Kupffer cells

Platelet activating factor (PAF) was found to stimulate the metabolism of inositol phospholipids via deacylation and phospholipase C in Kupffer cells, the resident macrophages in liver. PAF-induced phosphoinositide metabolism occurred in two phases. Within seconds after stimulation, in the absence of extracellular Ca++, platelet activating factor caused the phosphodiester hydrolysis of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-phosphate with the release of inositol 1,4,5-trisphosphate and inositol 1,4-bisphosphate. This was followed by an extracellular Ca(++)-dependent release of glycerophosphoinositol, inositol monophosphates and inositol bisphosphates. Various Ca(++)-mobilizing agonists failed to evoke hydrolysis of phosphoinositides. Platelet activating factor also stimulated the synthesis and release of prostaglandins from these cells. Platelet activating factor-stimulated phosphodiester metabolism of phosphoinositides and prostaglandin synthesis was inhibited by treatment with pertussis toxin and cholera toxin. Pertussis toxin also inhibited platelet activating factor-induced glycerophosphoinositol release. Cholera toxin, in contrast, stimulated platelet activating factor-induced glycerophosphoinositol release and prostaglandin synthesis and synergistically stimulated the effect of platelet activating factor on these processes. The results suggest that platelet activating factor-induced metabolism in the Kupffer cells occurs via specific receptors and may be mediated through the activation of different G-proteins.