The induction of glycogenolysis in the perfused liver by platelet activating factor is mediated by prostaglandin D2 from Kupffer cells.
Induction of glycogenolysis in the perfused liver by platelet activating factor (PAF) was blocked by the cyclooxygenase inhibitor indomethacin. 3H-labeled PAF was shown to interact in the perfused liver primarily with Kupffer cells. The addition of PAF to Kupffer cells resulted in a dose-dependent stimulation of prostaglandin D2 (PGD2) production, which was identified as the main eicosanoid formed after PAF stimulation of the Kupffer cells. PGD2 was able to induce a dose-dependent stimulation of glycogenolysis both in the perfused liver and in isolated parenchymal cells. The time-dependency of the PGD2 production and the glucose output by the perfused liver is consistent with a primary interaction of PAF with the Kupffer cells, followed by PGD2 formation, which subsequently stimulates glucose production in parenchymal cells.
Kuiper
J
J
Division of Biopharmaceutics, Sylvius Laboratories, University of Leiden, The Netherlands.
De Rijke
Y B
YB
Zijlstra
F J
FJ
Van Waas
M P
MP
Van Berkel
T J
TJ
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007728:Kupffer Cells / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D010972:Platelet Activating Factor / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000096:biosynthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; D006003:Glycogen; D005947:Glucose; D015230:Prostaglandin D2; D007213:Indomethacin