Platelet-activating factor-stimulated hepatic glycogenolysis is not mediated through cyclooxygenase-derived metabolites of arachidonic acid.
Platelet-activating factor (1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC)) is a potent lipid mediator which stimulates hepatic glycogenolysis, causes hepatic vasoconstriction, and stimulates the production of cyclooxygenase-derived metabolites of arachidonic acid, primarily prostaglandin (PG) D2 in the perfused liver. Following infusion of platelet-activating factor (1 nM) in the perfused rat liver the production of PGD2, measured in the effluent perfusate, increased 4-fold after only 2 min. Infusion of the cyclooxygenase inhibitor, ibuprofen (50 microM), abolished the stimulated production of PGD2 and thromboxane B2 in response to AGEPC without significantly affecting the hepatic glycogenolytic or vasoconstrictive responses to AGEPC. Contrary to previous reports, these observations do not support the suggestion that cyclooxygenase-derived metabolites mediate directly either the glycogenolytic or the vasoactive effects of AGEPC in the perfused rat liver.
Lapointe
D S
DS
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760.
Olson
M S
MS
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007052:Ibuprofen / Q000494:pharmacology; D008099:Liver / Q000187:drug effects; D008102:Liver Circulation / Q000187:drug effects; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013929:Thromboxane B2 / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects
D001095:Arachidonic Acids; D008112:Liver Glycogen; D010972:Platelet Activating Factor; D013929:Thromboxane B2; D011451:Prostaglandin-Endoperoxide Synthases; D005947:Glucose; D015230:Prostaglandin D2; D007052:Ibuprofen