Platelet-activating factor-mediated synthesis of prostaglandins in rat Kupffer cells.
Synthesis of prostaglandins was stimulated in rat Kupffer cells upon challenge with platelet-activating factor (PAF). PAF-mediated synthesis of prostaglandins was inhibited by the Ca2+ ion chelator (EGTA), the Ca2+ channel antagonist (nifedipine) and U66985, a structural analogue and antagonist of the biological effects of PAF in other cellular systems. Inhibitors of protein kinase C, staurosporine and polymixin B, did not affect PAF-induced prostaglandin synthesis. Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, stimulated synthesis of prostaglandins in Kupffer cells; PAF and PMA exerted additive actions on this process. Both PAF- and PMA-stimulated prostaglandin production was inhibited by TMB-8. PAF-stimulated synthesis of prostaglandins also was inhibited upon treatment of Kupffer cells with pertussis toxin. Cholera toxin, in contrast, stimulated the production of prostaglandins in a concentration-dependent manner; cholera toxin and PAF together had an additive effect. These results suggest that PAF-induced synthesis of prostaglandins is stimulated via a specific receptor coupled to a pertussis toxin-sensitive G-protein, is dependent upon extracellular Ca2+ and is not influenced by protein Kinase C activation. Since PAF and prostaglandins are produced in the liver under conditions such as endotoxemia, PAF-mediated synthesis of these lipid autacoids may be of importance in the regulation of hepatic function during pathophysiological episodes.
Gandhi
C R
CR
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760.
DeBuysere
M S
MS
Olson
M S
MS
D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D004789:Enzyme Activation; D007052:Ibuprofen / Q000494:pharmacology; D007728:Kupffer Cells / Q000378:metabolism*; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000502:physiology*; D011453:Prostaglandins / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001427:Bacterial Toxins; D010972:Platelet Activating Factor; D011453:Prostaglandins; D009637:Masoprocol; D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium; D007052:Ibuprofen