Induction of rat alpha-1-acid glycoprotein by phenobarbital is independent of a general acute-phase response. 1994

T Fournier, and R Vranckx, and N Mejdoubi, and G Durand, and D Porquet
Laboratoire de Biochimie Générale Faculté de Pharmacie, Chatenay-Malabry, France.

Phenobarbital (PB) induces transcription of the alpha 1-acid glycoprotein (AGP) gene, one of the major positive acute-phase proteins, the expression of which is controlled by a specific combination of glucocorticoids and cytokines. This raises questions as to the involvement of glucocorticoids and cytokine pathways in the PB-mediated effect on AGP gene expression. We found that the pattern of whole-serum proteins in PB-treated rats differed markedly from that observed during a typical acute inflammatory response (in turpentine-treated rats): levels of some positive acute-phase proteins (APP) increased slightly (alpha 1-acid glycoprotein, haptoglobin, hemopexin and T-kininogen), while levels of alpha 2 macroglobulin, the most sensitive marker of the acute-phase reaction, decreased. Among the negative APP, neither albumin nor prealbumin decreased while CBG increased. The cytokines involved in AGP gene regulation (mainly IL1, IL6 and TNF alpha) do not therefore seem to mediate the effect of PB on acute-phase protein expression. Glucocorticoid involvement is also ruled out by the observed enhancement of the effect of PB on AGP expression in adrenalectomized animals. Our results suggest that phenobarbital acts on AGP expression by a mechanism independent of the inflammatory pathway.

UI MeSH Term Description Entries
D008297 Male Males
D009961 Orosomucoid Acid Seromucoid,Seromucoid,Serum Sialomucin,alpha 1-Acid Glycoprotein,alpha 1-Acid Seromucoid,A(1)-Acid Seromucoid,Acid alpha 1-Glycoprotein,Alpha(1)-Acid Glycoprotein,alpha 1-Acid Glycoprotein (Acute Phase),alpha 1-Glycoprotein Acid,Acid alpha 1 Glycoprotein,Glycoprotein, alpha 1-Acid,Seromucoid, Acid,Seromucoid, alpha 1-Acid,Sialomucin, Serum,alpha 1 Acid Glycoprotein,alpha 1 Acid Seromucoid,alpha 1 Glycoprotein Acid
D010634 Phenobarbital A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D005938 Glucocorticoids A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. Glucocorticoid,Glucocorticoid Effect,Glucorticoid Effects,Effect, Glucocorticoid,Effects, Glucorticoid
D000210 Acute-Phase Reaction An early local inflammatory reaction to insult or injury that consists of fever, an increase in inflammatory humoral factors, and an increased synthesis by hepatocytes of a number of proteins or glycoproteins usually found in the plasma. Acute Phase Response,Acute-Phase State,Reaction, Acute-Phase,Response, Acute-Phase,Acute Phase Reaction,Acute Phase Responses,Acute Phase State,Acute-Phase Response,Phase Response, Acute,Reaction, Acute Phase,Response, Acute Phase,State, Acute-Phase
D000315 Adrenalectomy Excision of one or both adrenal glands. (From Dorland, 28th ed) Adrenalectomies
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014156 Transcortin A serpin family member that binds to and transports GLUCOCORTICOIDS in the BLOOD. Corticosteroid-Binding Globulin,Serpin A6,Corticosteroid Binding Globulin

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