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PAF effects on transmembrane signaling pathways in rat kupffer cells
Author(s) -
Gandhi Chandrashekhar R.,
Olson Merle S.
Publication year - 1991
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02536498
Subject(s) - platelet activating factor , cholera toxin , phosphatidylinositol , inositol , pertussis toxin , chemistry , lysophosphatidic acid , inositol phosphate , biochemistry , prostaglandin , extracellular , endocrinology , signal transduction , receptor , biology , g protein
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.