title: Effects of exogenous phospholipase enzymes, arachidonic acid and 1-oleoyl-2-acetyl-sn-glycerol on ketogenesis in isolated rat hepatocytes.
abstract: Studies were conducted to see whether exogenous phospholipase C from Clostridium perfringens, phospholipase A2 from Crotalus adamanteus venom, arachidonic acid and 1-oleoyl-2-acetyl-sn-glycerol (OAG) mimic the anti-ketogenic action of vasopressin in isolated rat hepatocytes. Exogenous phospholipase C inhibited ketogenesis in the presence of 0.5 mM oleate. Experiments employing [1-14C]oleate, however, indicated that the mechanism involved in the anti-ketogenic action of exogenous phospholipase C is distinct from that of vasopressin. The decreased rate of the production of acid-soluble products from [1-14C]oleate in response to vasopressin could be explained by the sum of the increased rates of 14CO2 formation and [1-14C]oleate esterification. By contrast, exogenous phospholipase C suppressed not only the formation of acid-soluble products but also 14CO2 production and [1-14C]oleate esterification. Indeed, phospholipase C greatly inhibited [1-14C]oleate uptake into hepatocytes. It is suggested that the alteration of the architecture of plasma membrane by exogenous phospholipase C may lead to the disturbance of oleate uptake and consequent general suppression of oleate metabolism. Exogenous phospholipase A2, arachidonic acid and OAG increased ketogenesis regardless of the presence of oleate. The ketogenic effects may be attributed to the supply of fatty acids by these agents to hepatocytes.
authors.affiliation: Department of Pharmacology, Fujita-Gakuen Health University School of Medicine, Aichi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Chihara
authors.forename: T
authors.initials: T
authors.lastname: Nomura
authors.forename: M
authors.initials: M
authors.lastname: Tachibana
authors.forename: H
authors.initials: H
authors.lastname: Nomura
authors.forename: Y
authors.initials: Y
authors.lastname: Nomura
authors.forename: Y
authors.initials: Y
authors.lastname: Hagino
mesh_terms: D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002245:Carbon Dioxide / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004951:Esterification; D005947:Glucose / Q000378:metabolism; D005989:Glycerides / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects; D007657:Ketone Bodies / Q000096:biosynthesis*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010084:Oxidation-Reduction; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D010738:Type C Phospholipases / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
chemical_list: D001095:Arachidonic Acids; D004075:Diglycerides; D005989:Glycerides; D007657:Ketone Bodies; D009829:Oleic Acids; D014667:Vasopressins; D002245:Carbon Dioxide; D016718:Arachidonic Acid; D019301:Oleic Acid; C038237:1-oleoyl-2-acetylglycerol; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D005947:Glucose; D002118:Calcium