Abstract
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 Ca 2+ ion chelator (EGTA), the Ca 2+ 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 Ca 2+ 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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.