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.
Gandhi
C R
CR
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284.
Olson
M S
MS
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011453:Prostaglandins / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000187:drug effects*; D014667:Vasopressins / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D010972:Platelet Activating Factor; D011453:Prostaglandins; D010566:Virulence Factors, Bordetella; D014667:Vasopressins; D004533:Egtazic Acid; D002772:Cholera Toxin; D037342:Pertussis Toxin; D009543:Nifedipine; D001920:Bradykinin; D002118:Calcium; D009638:Norepinephrine