title: PGE(2) stimulates O(2) uptake in hepatic parenchymal cells: involvement of the cAMP-dependent protein kinase.
abstract: The aim of this study was to determine which PGE(2) receptors and signal transduction pathways are responsible for the stimulation of oxygen uptake in liver. Hepatic parenchymal cells isolated from female Sprague-Dawley rats were incubated either with PGE(2), 17-phenyl-omega-trinor PGE(2) (an EP(1)-specific agonist), or 11-deoxy PGE(1) (an EP(2)/EP(4)-specific agonist), and oxygen consumption was measured. Both PGE(2) and 11-deoxy PGE(1) stimulated oxygen consumption. However, an EP(1) agonist was without effect. Although PGE(2) elevated intracellular calcium, this occurred at concentrations approximately 500-fold lower than that required to stimulate oxygen uptake. PGE(2)-stimulated increases in cAMP formation correlated well with the increase in oxygen consumption. Dibutyryl cAMP also increased oxygen consumption. Furthermore, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide, a cell-permeable inhibitor of protein kinase A (PKA), reduced the stimulation of oxygen uptake by PGE(2). Incubation of isolated parenchymal cell mitochondria with the purified catalytic subunit of PKA and ATP increased both state 3 rates of oxygen uptake and the respiratory control ratio by approximately 50%. Activation of these events was prevented by incubation with the PKA inhibitory peptide, PKI. These findings are consistent with the hypothesis that PGE(2) stimulates oxygen consumption via an EP(2) and/or EP(4) subclass of receptors through the actions of cAMP on a cAMP-dependent protein kinase.
authors.affiliation: Laboratory of Hepatobiology, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365, USA.
authors.forename: W
authors.initials: W
authors.lastname: Qu
authors.forename: L M
authors.initials: LM
authors.lastname: Graves
authors.forename: R G
authors.initials: RG
authors.lastname: Thurman
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004579:Electron Transport / Q000502:physiology; D005260:Female; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D010100:Oxygen / Q000493:pharmacokinetics*; D010101:Oxygen Consumption / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019802:Succinic Acid / Q000494:pharmacology
chemical_list: C092396:17-phenyltrinorprostaglandin E2; D000897:Anti-Ulcer Agents; D010726:Phosphodiesterase Inhibitors; D018078:Receptors, Prostaglandin E; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000244:Adenosine Diphosphate; D003994:Bucladesine; D019802:Succinic Acid; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000527:Alprostadil; D015232:Dinoprostone; D010100:Oxygen; D015056:1-Methyl-3-isobutylxanthine; C034008:11-deoxyprostaglandin E1