Inhibition of Glucagon‐Stimulated Glycogenolysis by S‐Nitroso‐N‐acetylpenicillamine*

Brass, Eric P.; Vetter, W

doi:10.1111/j.1600-0773.1993.tb01346.x

Cited by 20 publications

(17 citation statements)

References 32 publications

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“…This observation agrees with the findings that the inhibition of NOS by L-NAME in cultured hepatocytes increases the intracellular levels of glycogen (Donato et al 2001), and that NO donors such as S-nitroso-N-acetylpenicillamine (SNAP) inhibit the biosynthesis of glycogen (Sprangers et al 1998) and may cause discreet inhibition of glycogenolysis stimulated by glucagon (Brass and Vetter 1993). In contrast, Hropot et al (2003) have observed that treatment of rats with L-NAME (25 mg/rat per day for 6 weeks) decreases the content of glycogen, ATP, and creatine phosphate in cardiac tissue, and Kitano et al (2002) have reported that NO has little effect on glycogen synthesis by hepatocytes.…”

Section: Discussionsupporting

confidence: 88%

Hepatic morphological alterations, glycogen content and cytochrome P450 activities in rats treated chronically with Nω-nitro-L-arginine methyl ester (L-NAME)

et al. 2007

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Chronic treatment of rats with N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) biosynthesis, results in hypertension mediated partly by enhanced angiotensin-I-converting enzyme (ACE) activity. We examined the influence of L-NAME on rat liver morphology, on hepatic glycogen, cholesterol, and triglyceride content, and on the activities of the cytochrome P450 isoforms CYP1A1/2, CYP2B1/2, CYP2C11, and CYP2E1. Male Wistar rats were treated with L-NAME (20 mg/rat per day via drinking water) for 2, 4, and 8 weeks, and their livers were then removed for analysis. Enzymatic induction was produced by treating rats with phenobarbital (to induce CYP2B1/2), beta-naphthoflavone (to induce CYP1A1/2), or pyrazole (to induce CYP2E1). L-NAME significantly elevated blood pressure; this was reversed by concomitant treatment with enalapril (ACE inhibitor) or losartan (angiotensin II AT(1) receptor antagonist). L-NAME caused vascular hypertrophy in hepatic arteries, with perivascular and interstitial fibrosis involving collagen deposition. Hepatic glycogen content also significantly increased. L-NAME did not affect fasting glucose levels but significantly reduced insulin levels and increased the insulin sensitivity of rats, based on an intraperitoneal glucose tolerance test. Immunoblotting experiments indicated enhanced phosphorylation of protein kinase B and of glycogen synthase kinase 3. All these changes were reversed by concomitant treatment with enalapril or losartan. L-NAME had no effect on hepatic cholesterol or triglyceride content or on the basal or drug-induced activities and protein expression of the cytochrome P450 isoforms. Thus, the chronic inhibition of NO biosynthesis produced hepatic morphological alterations and changes in glycogen metabolism mediated by the renin-angiotensin system. The increase in hepatic glycogen content probably resulted from enhanced glycogen synthase activity following the inhibition of glycogen synthase kinase 3 by phosphorylation.

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Section: Discussionsupporting

confidence: 88%

Hepatic morphological alterations, glycogen content and cytochrome P450 activities in rats treated chronically with Nω-nitro-L-arginine methyl ester (L-NAME)

et al. 2007

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“…Finally, L-canavanine may also have improved energy production by its favorable effects on the endotoxininduced hypoglycemia. Recent studies have reported that this hypoglycemia is largely mediated by NO overproduction, both through a decrease in glucose production, related to inhibition of neoglucogenesis (38,39) and glycogenolysis (40), and an increase in glucose utilization by stimulated macrophages (41).…”

Section: Effects Of L-canavaninementioning

confidence: 99%

L-canavanine improves organ function and tissue adenosine triphosphate levels in rodent endotoxemia.

Liaudet

Fishman²,

Markert³

et al. 1997

Am J Respir Crit Care Med

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Overproduction of NO by an inducible NO synthase (iNOS) plays a major role in the pathophysiology of septic shock, and selective inhibition of iNOS in this setting could be of great therapeutic value. In the present study, we evaluated the effects of L-canavanine, a selective iNOS inhibitor, in an animal model of septic shock, with a particular focus on tissue oxidative metabolism and organ functions. Anesthetized rats challenged intravenously with lipopolysacharide (LPS) were treated after 1 h by a continuous infusion of either L-canavanine (20 mg/kg/h; n = 11) or an equivalent volume of saline (2 ml/kg/h; n = 17) given for 4 h. A third group (sham rats; n = 9) did not receive LPS and was treated with a continuous infusion of saline (2 ml/kg/h). At the end of experiments, biopsies were taken from the liver, the kidney, and the small intestine for the measurement of tissue ATP. LPS induced a progressive fall in blood pressure, accompanied by biologic signs of liver and kidney failure, concomitant with a marked decrease in tissue ATP stores. L-canavanine largely prevented hypotension and significantly increased tissue ATP while reducing the signs of organ dysfunction. These effects were associated with a significant improvement in survival during the 5 h of study. We conclude that L-canavanine not only reduces hypotension in endotoxin shock but also largely prevents the detrimental consequences of LPS on tissue oxidative metabolism and major organ functions, allowing a decrease in endotoxin lethality.

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“…Our original experimental protocol was modified from the steady state determination of receptor concentrations via Western blot (11) to the measurement of biosynthesis rate by pulse labeling with [ 35 S]Met/Cys. This change in protocol allowed the reduction of 8-Br-cGMP and atrial natriuretic factor (ANF) concentrations used in the present experiments to the level previously employed by others in short term protocols in cultured or isolated hepatocytes (25)(26)(27)(28)(29). HuH-7 cells were grown to near-confluence in MEM supplemented with either 10% FBS or 10% dFBS to which 10 to 1000 M 8-Br-cGMP, 10 nM ANF, or 100 M sodium nitroprusside (SNP) (shown to produce nitric oxide (25), an activator of soluble guanylate cyclase (29)) were added (Fig.…”

Section: Short Term Cgmp-regulated Expression Of Asgr-basedmentioning

confidence: 99%

“…1A). Within 1 h of the addition of 500 M 8-Br-cGMP and activators of both the particulate (ANF) and soluble (SNP) guanylate cyclases (25)(26)(27)(28)(29), the biosynthetic rate of ASGR was increased by 6. tained in MEM supplemented with FBS or dFBS with or without 8-Br-cGMP or its inducers (Fig. 1B).…”

Section: Short Term Cgmp-regulated Expression Of Asgr-basedmentioning

confidence: 99%

Cytoplasmic Protein mRNA Interaction Mediates cGMP-modulated Translational Control of the Asialoglycoprotein Receptor

Stockert

Ren

1997

Journal of Biological Chemistry

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Expression of the asialoglycoprotein receptor by the human hepatocellular carcinoma cell line HuH-7 in response to intracellular cGMP concentrations was previously shown to be regulated at the translational level. In a cell-free system, initiation of asialoglycoprotein receptor mRNA translation was dependent on the presence of the 7-methylguanylate cap site and was independent of 8-bromo-cGMP levels in which the cells were grown prior to RNA isolation. Stable transfection of COS-7 cells with deletion constructs of the asialoglycoprotein receptor H2b subunit localized the cGMP-responsive cisacting element to the mRNA 5 -untranslated region (UTR). Addition of biotin (an activator of guanylate cyclase) induced the expression of ␤-galactosidase present as a chimeric plasmid containing the H2b 187-nucleotide 5 -UTR. An RNA gel retardation assay identified a 37-nucleotide cognate sequence within this 187-nucleotide region. Titration of the 5 -UTR with a cytosolic fraction isolated from HuH-7 grown in the presence or absence of 8-bromo-cGMP or biotin provided direct evidence for an RNA-binding protein responsive to intracellular levels of cGMP. Based on these findings, it seems reasonable to propose that reduction of intracellular levels of cGMP by biotin deprivation results in a negative trans-acting factor associating with the 5 -UTR of asialoglycoprotein receptor mRNAs, thereby inhibiting translation.

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Inhibition of Glucagon‐Stimulated Glycogenolysis by S‐Nitroso‐N‐acetylpenicillamine*

Cited by 20 publications

References 32 publications

Hepatic morphological alterations, glycogen content and cytochrome P450 activities in rats treated chronically with Nω-nitro-L-arginine methyl ester (L-NAME)

Hepatic morphological alterations, glycogen content and cytochrome P450 activities in rats treated chronically with Nω-nitro-L-arginine methyl ester (L-NAME)

L-canavanine improves organ function and tissue adenosine triphosphate levels in rodent endotoxemia.

Cytoplasmic Protein mRNA Interaction Mediates cGMP-modulated Translational Control of the Asialoglycoprotein Receptor

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