Glucose release as a response to glucagon in rat hepatocyte culture: involvement of NO signaling.
Glucagon and alpha-adrenergic-induced glycogenolysis is realized via the agonist/adenylyl cyclase/cAMP/protein kinase signaling pathway or via the activation of phosphorylase kinase by the mobilized calcium that supports the inhibition of glycogen synthase, respectively. The role of nitric oxide (NO) in this process has not been extensively studied. The present work was directed to the question whether NO is produced during glucagon-induced glycogenolysis in rat hepatocyte in a similar way like alpha-adrenoceptor stimulation. Glycogen-rich hepatocyte cultures were used. NO production (NO(2)(-)) was assessed under the influence of glucagon, dibutyryl cyclic AMP (db-cAMP), forskolin, the nitric oxide synthase (NOS) inhibitors N(omega)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine, and the NO donor S-nitroso-N-acetyl penicillamine (SNAP). Inducible NOS (iNOS) mRNA was examined by reverse transcription-polymerase chain reaction. Glycogenolysis was followed up by estimation of medium glucose levels. The amount of glucose and NO(2)(-) released by glycogen-rich hepatocytes was increased as a result of glucagon, db-cAMP, forskolin and SNAP treatments. iNOS gene expression was upregulated by glucagon. Glycogenolysis that occurs through glucagon receptor stimulation involves NO production downstream of transduction pathways through an isoform of NO synthase. The present and previous studies document possible involvement of NO signaling in glycogenolytic response to glucagon and adrenergic agonists in hepatocytes.
Farghali
H
H
Institute of Pharmacology, First Faculty of Medicine, Charles University, Prague, Czech Republic. hfarg@lf1.cuni.cz
Hodis
J
J
Kutinová-Canová
N
N
Potmesil
P
P
Kmoníčková
E
E
Zídek
Z
Z
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002469:Cell Separation; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis; D006146:Guanidines / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*
D006146:Guanidines; D020030:Nitric Oxide Donors; D005576:Colforsin; D009569:Nitric Oxide; D003994:Bucladesine; D026423:S-Nitroso-N-Acetylpenicillamine; D006003:Glycogen; D005934:Glucagon; D052247:Nitric Oxide Synthase Type II; D005947:Glucose; C004479:pimagedine