title: The role of adrenergic agonists on glycogenolysis in rat hepatocyte cultures and possible involvement of NO.
abstract: Certain liver metabolic diseases point to the presence of disturbances in glycogen deposition. Epinephrine raises the cAMP level that activates protein kinase A leading to the activation of phosphorylase and glycogen breakdown. In the present report, we sought to investigate whether NO is produced during adrenoceptor agonist-induced glycogenolysis in rat hepatocytes in cultures. Isolated glycogen rich rat hepatocytes in cultures were used. NO production (NO(2)(-)) was assessed under the effect of adrenergic agonists and adrenergic agonist/antagonist pairs, dibutyryl cyclic AMP sodium-potassium salt (db-cAMP), NO synthase (NOS) inhibitors N(omega)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG) and the NO donor S-nitroso-N-acetyl penicillamine (SNAP). The inducible NO synthase (iNOS) mRNA was examined by the reverse transcription-polymerase chain reaction (RT-PCR). Glycogenolysis was quantified by glucose levels released into medium. The amount of glucose and NO(2)(-) released by hepatocytes was increased as a result of epinephrine, phenylephrine or db-cAMP treatments. The increase in glucose and NO(2)(-) released by epinephrine or phenylephrine was blocked or reduced by prazosin pretreatment and by NOS inhibitors aminoguanidine and L-NAME. iNOS gene expression was up-regulated by epinephrine. It can be concluded that glycogenolysis occurs through -adrenoceptor stimulation and a signaling cascade may involve NO production.
authors.affiliation: Institute of Pharmacology; First Faculty of Medicine, Charles University, Prague, Czech Republic. hodik@volny.cz
authors.forename: J
authors.initials: J
authors.lastname: Hodis
authors.forename: N
authors.initials: N
authors.lastname: Kutinová-Canová
authors.forename: P
authors.initials: P
authors.lastname: Potmesil
authors.forename: L
authors.initials: L
authors.lastname: Kameníková
authors.forename: E
authors.initials: E
authors.lastname: Kmoníčková
authors.forename: Z
authors.initials: Z
authors.lastname: Zídek
authors.forename: H
authors.initials: H
authors.lastname: Farghali
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003563:Cyclic CMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D050261:Glycogenolysis / Q000187:drug effects*; D006146:Guanidines / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D010656:Phenylephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000187:drug effects* / Q000378:metabolism; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D006146:Guanidines; D020030:Nitric Oxide Donors; D011941:Receptors, Adrenergic; D010656:Phenylephrine; D009569:Nitric Oxide; D003563:Cyclic CMP; C053441:dibutyryl cyclic-3',5'-cytidine monophosphate; D026423:S-Nitroso-N-Acetylpenicillamine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005947:Glucose; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester; D011224:Prazosin; D004837:Epinephrine