Modulation of prostaglandin E2 catabolism and action by fuel substrates in rat hepatocytes.
The hepatic level of prostaglandins will reflect the balance between synthesis of prostaglandins and their rapid catabolism via beta-oxidation by hepatocytes. In the present study we examined the effect of physiological fuel substrates on the breakdown and action of prostaglandin E2 (PGE2) in isolated rat hepatocytes. Palmitic acid (0.32 mM), a long-chain fatty acid, inhibited the rate of PGE2 breakdown (10(-7) M) by approx. 80%. As the palmitic acid concentration was increased from 0 to 0.8 mM, the percentage of PGE2 remaining in the incubation 5 min following prostaglandin addition was raised from approx. 10% to over 98%. Octanoic acid (0.8 mM) also inhibited PGE2 catabolism, while butyric acid (0.8 mM) and pyruvic acid (2.5 mM) were without effect. The inhibition of glucagon-stimulated glycogenolysis by PGE2 was increased in the presence of 0.6 mM palmitic acid, consistent with decreased PGE2 catabolism. These studies demonstrate that changes within the range of free fatty acid concentrations seen physiologically in vivo may dramatically alter PGE2 catabolism and, therefore, the effect of PGE2 to modulate hormonal action in the liver.
Brass
E P
EP
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.
Garrity
M J
MJ
D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002210:Caprylates / Q000494:pharmacology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism*; D005934:Glucagon / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology*; D011773:Pyruvates / Q000494:pharmacology*; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D002087:Butyrates; D002210:Caprylates; D008112:Liver Glycogen; D010169:Palmitic Acids; D011773:Pyruvates; D020148:Butyric Acid; D019308:Palmitic Acid; D019289:Pyruvic Acid; D005934:Glucagon; D015232:Dinoprostone; C031492:octanoic acid