Opposite effects of low and high doses of arginine on glutamate-induced nitric oxide formation in rat substantia nigra

Castellano, Miguel A.; Rojas-Dı́az, David; Martín, Felipe A; Quintero, Miguel; Alonso, Josefina; Navarro, Eduardo; González–Mora, José Luis

doi:10.1016/s0304-3940(01)02295-9

Cited by 21 publications

(14 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…26) Usually, these 2 pathways compete with the same substrate arginine, 27,28) and it has been suggested that activated arginase downregulates NO production in preventing NO-mediated apoptosis in activated macrophages. 29) In this study, we found that a medium dose of L-NAME may significantly elevate plasma ornithine but not citrulline (Table 4).…”

Section: Discussionmentioning

confidence: 99%

Dose Effects of Chronically Infused Nitric Oxide Synthase Inhibitor NG-Nitro-L-arginine Methyl Ester on Anabolic Response and Arginine Metabolism in Rats with Subacute Peritonitis

Hsiao

Lee

Tsao

et al. 2011

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Patients with peritonitis develop arginine deficiency due to decreased consumption, impaired absorption, and increased utilization of arginine.1,2) Arginine, a precursor for the synthesis of nitric oxide (NO), urea, creatinine, glutamate, proline, and polyamines, is a conditionally essential amino acid in stressed conditions, especially in inflammation. 1,3,4) Green et al. 5) was the first research group to show that nitrate/nitrite concentrations and the severity of infection are closely correlated. Subsequent studies showed that patients with peritonitis have uncontrolled activation of inducible nitric oxide synthase (NOS), which results in NO overproduction and the following sepsis.6) Therefore, inhibition of NOS might be a useful strategy to treat arginine deficiency and inhibit excess NO production. 6,7) In animal and human studies, the results of NOS inhibition in inflammation have been ambiguous. For example, N G -nitro-L-arginine methyl ester (L-NAME), a nonselective NOS inhibitor which inhibits both constitutive and inducible NOS, effectively ameliorated the inflammatory lesions in the skin of zinc-deficient rats, 8) improved the myocardial function in sepsis, 9) and attenuated the lipopolysaccharide-induced peritoneal permeability and NO release in mice.10) On the contrary, some studies have shown that L-NAME may cause hypertension, augment the expressions of interferon (IFN)-g and interleukin (IL)-2, and result in markedly severe disease in rats with T cell-dependent autoimmune interstitial nephritis.11) The adverse effects of NOS inhibitors have also been observed in subjects with hemodynamic instability and sepsis. [12][13][14] Evidence suggests that the therapeutic effects of NOS inhibitors may depend on the dose, timing, and the severity and category of diseases.In clinical practice, a number of in hospital patients with subacute peritonitis developed chronic malnutrition and inflammation. Administration of total parenteral nutrition solution is an efficient method to supply all daily nutrition requirements; however, it is associated with occurrence of increased complicated infections.15) Zheng et al. 16) indicated that long-term parenteral nutrition-induced liver steatosis may be attenuated by L-NAME administration. Up to now, only few reports have described the long-term application of L-NAME for subacute peritonitis. Additionally, no study has ever addressed the effects of L-NAME on the inflammatory response and amino acid metabolism in subjects administered parenteral nutrition. In our study, we used a rat model with subacute peritonitis induced by cecal puncture and administered total parenteral nutrition solution to provide adequate nutrition, and we investigated the dose effects of parenterally supplemented L-NAME on the anabolism, inflammatory response, and arginine-derived metabolites such as the intermediates of the urea cycle, circulating profile of amino acids, NO, and cytokines. MATERIALS AND METHODS Animals and Experimental DesignMale Wistar rats (8-9 weeks old), initially weighi...

show abstract

Section: Discussionmentioning

confidence: 99%

Dose Effects of Chronically Infused Nitric Oxide Synthase Inhibitor NG-Nitro-L-arginine Methyl Ester on Anabolic Response and Arginine Metabolism in Rats with Subacute Peritonitis

Hsiao

Lee

Tsao

et al. 2011

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…Available literature data suggest that L-arginine may not only increase, but also decrease NO synthesis [2,3], and NO overproduction decreases the NO-synthase activity [14]. In our case, it was shown that the inhibitory effect of L-arginine was not cancelled by NO-synthase blockers and, consequently, this effect is not directly connected with NO synthesis.…”

Section: Inhibitors Of No Synthesis Do Not Suppress the Inhibitory Efmentioning

confidence: 41%

“…However, it was shown recently in different experimental models that the role of L -arginine in the functioning of the NO system is ambiguous. The effects of L -arginine are not always associated with enhancement of NO synthesis [2,3] and may coincide with the effects of NO-synthase and guanylate cyclase (GC) inhibitors rather than NO [4]. Mechanisms of this "inadequate" effect of L -arginine are not clear.…”

mentioning

confidence: 99%

Neuronal effects of L-arginine not associated with synthesis of nitric oxide

D'yakonova

2005

Dokl Biol Sci

View full text Add to dashboard Cite

L -arginine is a substrate for enzymatic synthesis of nitric oxide (NO) and is widely used in experiments to increase the level of endogenous NO. The effects of L -arginine, as a rule, are similar to those of NO and NO donors [1]. However, it was shown recently in different experimental models that the role of L -arginine in the functioning of the NO system is ambiguous. The effects of L -arginine are not always associated with enhancement of NO synthesis [2, 3] and may coincide with the effects of NO-synthase and guanylate cyclase (GC) inhibitors rather than NO [4]. Mechanisms of this "inadequate" effect of L -arginine are not clear. I addressed this problem in a study on the serotonin neurons of the brain of the snail Helix pomatia. It is well known that invertebrates, including mollusks, have the same neurochemistry and regulatory functions of NO as vertebrates (e.g., [5,6]), which allows molluscan neurons to be used as a convenient object to study the mechanisms of the functioning of the NO system on the cellular level. Earlier, we showed that NO excited serotonin neurons of snails and tonically enhanced their activity [7][8][9]. The results of this work indicate that L -arginine has the opposite (inhibitory) effect on the same neurons and decreases the excitatory effects of NO donors on these neurons and that this effect of L -arginine is due to the suppression of the GC activity by L -arginine.This work was performed on serotonin neurons of the dorsal surface of the parietal and visceral ganglia of the H. pomatia brain (on the location and properties of these neurons, see [7,10]). For electrophysiological studies by microelectrode technique, isolated brains of snails were treated with 2.5 mg/ml protease (Sigma, United States) for 10-15 min, cleaned from envelopes, and fixed on a silgart base in a chamber. Glass microelectrodes (20-30 M Ω ) were filled with 3 M KCl. Part of the experiments were performed using isolated neurons, which were pulled out the ganglion by means of a microelecrode by the method described earlier [11].L -arginine ( L -arginine hydrochloride); D-arginine (D-arginine hydrochloride); the donors of nitric oxide SNAP (S-nitro-N-acetylpenicillamine), sodium nitroprusside (SNP) and sodium nitrate; the inhibitors of NO-synthase L -NNA ( L -nitro-L -arginine) and 7-NI (7-nitroindazole); the inhibitor of guanylate cyclase methylen blue; and the membrane-permeable analog of cGMP db-cGMP (dibutyryl-cGMP) (all compounds from Sigma, United States) were used in the experiments. The compounds were added into the flow or the chamber with a micropipette. In the experiments, neuronal activity was recorded for 2-3 min before and after the application of compounds. The final result was assessed as the mean number of action potentials (APs) during 10 s of the record. Statistical data are presented in the text as the mean + standard error of the mean. Opposite effects of L -arginine and NO donors on serotonin neurons.Most of the experiments were carried out using four neurons: two neurons from the visceral...

show abstract

“…L-arginine increases arginase activity, which could decrease NO production by NOS [18] via reducing substrate availability [33]. In addition, decarboxylation of L-arginine by the arginine decarboxylase produces agmatine [34], which is a competitive inhibitor of the NOS isoenzymes [35] and could inhibit all isoforms of NOS and NO production [36,37]. While there are several reports of the protective effect of L-arginine administration against development of gastric mucosal lesion [2], it has recently been reported that L-arginine metabolism could impair antimicrobial NO synthesis in stomach and cause H. pylori induced DNA damage [38].…”

Section: Discussionmentioning

confidence: 99%

Nitrate/L-arginine Therapy and Nitric Oxide Levels in the Stomach and Liver of Rats

Mehrazin

Ghasemi

Zahediasl

2015

Zahedan J Res Med Sci

View full text Add to dashboard Cite

Background:The L-arginine/nitric oxide (NO) pathway is a major defensive system in gastric mucosa. Nitrate can restore NO homeostasis when enzymatic NO production becomes dysfunctional. Objectives: The aim of this study was to investigate the effects of nitrate/L-arginine administration on NO levels in the stomach and liver of rats. Materials and Methods: In this interventional study, adult male Wistar rats were divided into 3 groups of control, nitrate and L-arginine (n = 8). Rats in the nitrate and L-arginine groups were administered sodium nitrate (500 mg/L) or L-arginine (2%) for one week in drinking water while those in control group consumed tap water. At the end, serum, stomach and liver NO metabolite (NO x ) concentrations were measured by the Griess method. Conclusions: Nitrate and L-arginine administration had opposite effects on NO x levels in stomach and liver of normal rats. Increase in stomach NO x following nitrate administration may be due to gastric nitrate absorption, while the decrease in tissue NO x following L-arginine administration may be due to increase in arginase activity. These findings may be important considering current data on the protective roles of dietary nitrate/nitrite.

show abstract

Opposite effects of low and high doses of arginine on glutamate-induced nitric oxide formation in rat substantia nigra

Cited by 21 publications

References 15 publications

Dose Effects of Chronically Infused Nitric Oxide Synthase Inhibitor NG-Nitro-L-arginine Methyl Ester on Anabolic Response and Arginine Metabolism in Rats with Subacute Peritonitis

Dose Effects of Chronically Infused Nitric Oxide Synthase Inhibitor NG-Nitro-L-arginine Methyl Ester on Anabolic Response and Arginine Metabolism in Rats with Subacute Peritonitis

Neuronal effects of L-arginine not associated with synthesis of nitric oxide

Nitrate/L-arginine Therapy and Nitric Oxide Levels in the Stomach and Liver of Rats

Contact Info

Product

Resources

About