title: Increased bioavailability of enzymes of eicosanoid synthesis in hepatic and extrahepatic tissues after portacaval shunting.
abstract: Metabolites of arachidonic acid have been attributed to severe circulatory, metabolic and hormonal alterations in patients with chronic liver disease. In order to study changes of the tissue-specific availability of enzymes of eicosanoid synthesis, we used portacaval-shunted rats, as this model exhibits many clinical and biochemical similarities to patients suffering from cirrhosis of the liver. Microsomal mass and maximal velocity of prostaglandin H synthase, the initial enzyme of prostaglandin synthesis, were markedly and permanently increased after shunting in both hepatic and extrahepatic tissues as compared to those of sham-operated rats. Maximal velocity of thromboxane synthase and prostacyclin synthase, two more peripheral enzymes of the arachidonic acid cascade, were tissue-specifically enhanced, whereas the apparent affinities (Km) remained unchanged. Determination of 5-lipoxygenase activity in tissue preparations disclosed a preferential increase in the liver, lung and renal cortex after portacaval shunting. Furthermore, exposure to endotoxin closely mimicked the shunting-induced changes. These results suggest that after portacaval shunting and possibly in patients with advanced liver disease, profound abnormalities at the level of local enzyme expression might play a pathophysiologically important role in the control of eicosanoid synthesis.
authors.affiliation: Department of Internal Medicine, University of Heidelberg, Federal Republic of Germany.
authors.forename: M
authors.initials: M
authors.lastname: Goerig
authors.forename: H
authors.initials: H
authors.lastname: Wernze
authors.forename: B
authors.initials: B
authors.lastname: Kommerell
authors.forename: M
authors.initials: M
authors.lastname: Grün
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001682:Biological Availability; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004537:Eicosanoic Acids / Q000096:biosynthesis* / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology*; D008168:Lung / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D011167:Portacaval Shunt, Surgical; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000378:metabolism; D013931:Thromboxanes / Q000378:metabolism
chemical_list: D004537:Eicosanoic Acids; D013931:Thromboxanes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D011464:Epoprostenol; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone