Glial‐Neuronal Transfer of Arginine and <i>S</i>‐Nitrosothiols in Nitric Oxide Transmission

Q., Kim; Grima, G; Benz, Beatrix; Salt, Thomas E.

doi:10.1111/j.1749-6632.2002.tb04058.x

Cited by 21 publications

(10 citation statements)

References 82 publications

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“…Recent studies have demonstrated that arginine availability is an important condition for the physiological functioning of the nitroergic system (Do et al, 2002; and Saul'skaya, 2007). Indirect reports confirm the antioxidant effects of l-arginine in the early and late stages of ischaemia (Maksimovich et al, 2006) and its reduction in brain edema formation and improvement of cortical blood flow in the early phase after a brain trauma (Lundblad and Bentzer, 2007).…”

Section: Systemic Administrationsmentioning

confidence: 93%

Brain nitric oxide: Regional characterisation of a real-time microelectrochemical sensor

Finnerty¹,

O'Riordan²,

Pålsson³

et al. 2012

Journal of Neuroscience Methods

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. a b s t r a c tA reliable method of directly measuring endogenously generated nitric oxide (NO) in real-time and in various brain regions is presented. An extensive characterisation of a previously described amperometric sensor has been carried out in the prefrontal cortex and nucleus accumbens of freely moving rats. Systemic administration of saline caused a transient increase in signal from baseline levels in both the prefrontal cortex (13 ± 3 pA, n = 17) and nucleus accumbens (12 ± 3 pA, n = 8). NO levels in the prefrontal cortex were significantly increased by 43 ± 9 pA (n = 9) following administration of l-arginine. A similar trend was observed in the nucleus accumbens, where an increase of 44 ± 9 pA (n = 8) was observed when compared against baseline levels. Systemic injections of the non-selective NOS inhibitor l-NAME produced a significant decrease in current recorded in the prefrontal cortex (24 ± 6 pA, n = 5) and nucleus accumbens (17 ± 3 pA, n = 6). Finally it was necessary to validate the sensors functionality in vivo by investigating the effect of the interferent ascorbate on the oxidation current. The current showed no variation in both regions over the selected time interval of 60 min, indicating no deterioration of the polymer membrane. A detailed comparison identified significantly greater affects of administrations on NO sensors implanted in the striatum than those inserted in the prefrontal cortex and the nucleus accumbens.

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Section: Systemic Administrationsmentioning

confidence: 93%

Brain nitric oxide: Regional characterisation of a real-time microelectrochemical sensor

Finnerty¹,

O'Riordan²,

Pålsson³

et al. 2012

Journal of Neuroscience Methods

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“…At low arginine concentrations, neuronal NO synthase generates NO and superoxide, favouring the production of the toxin peroxynitrite. The NMDA-induced excitotoxicity in neuronal cells is therefore dependent on the arginine availability (Do et al, 2002).…”

Section: Cellular Mechanism Of Action Of Kynureninesmentioning

confidence: 99%

Role of Kynurenines in the Central and Peripherial Nervous Systems

Németh¹,

Toldi²,

Vécsei

2005

CNR

147

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Kynurenine (KYN) is an intermediate in the pathway of the metabolism of tryptophan to nicotinic acid. KYN is formed in the mammalian brain (40%) and is taken up from the periphery (60%), indicating that it can be transported across the blood-brain barrier (BBB). In the brain, KYN can be converted to two other components of the pathway: the neurotoxic quinolinic acid (QUIN) and the neuroprotective kynurenic acid (KYNA). QUIN is probably the most widely studied metabolite of KYN, because it may cause excitotoxic neuronal cell loss and convulsions by interacting with the N-methyl-D-aspartate (NMDA) receptor complex, a type of glutamate receptor. KYNA is another metabolite of KYN; its synthesis is catalysed by KYN aminotransferases. This is the only known endogenous NMDA receptor inhibitor, which can act at the glycine site on the receptor complex. Furthermore, KYNA non-competitively inhibits alpha7 nicotinic acetylcholine presynaptic receptors (nAChRs), inhibiting glutamate release, and regulates the expression of alpha4beta2 nAChR. It is well-known that the activation of excitatory amino acid (EAA) receptors can play a role in a number of neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, stroke and epilepsy. Various studies have been made of whether the EAA receptor antagonist KYNA can exert a therapeutic effect in these neurological disorders. It has been established that KYNA has only a very limited ability to cross the BBB. Other KYNA derivatives have been synthesised (e.g. glucosamine-KYNA, 4-chloro-KYNA and 7-chloro-KYNA), which are well transported across the BBB and act on the glutamate receptors. Moreover, it has been demonstrated that probenecid, a known inhibitor of the transport of organic acids (e.g. KYNA), increases the cerebral concentration of KYNA. There is another new perspective to the maintenance of a high level of KYNA in the brain: the use of enzyme inhibitors, which can block the synthesis of the neurotoxic QUIN. These are some of the most promising possibilities as novel therapeutic strategies for the treatment of neurodegenerative diseases, in which the hyperactivation of amino acid receptors could be involved. The presence and importance of KYN derivatives in the periphery are also discussed in the light of recent publications.

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“…At low arginine concentration, neuronal NO synthase generates NO and superoxide, favouring the production of the toxin peroxynitrite. Thus, the NMDA-induced excitotoxicity in neuronal cells is dependent on the arginine availability [72].…”

Section: Quin and 3-hydroxy-ana Oxygenasementioning

confidence: 99%

Neuromodulation of Hippocampal Synaptic Plasticity, Learning, and Memory by Noradrenaline

Gelinas¹,

Nguyen

2007

CNSAMC

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The intermediates of the kynurenine pathway, called kynurenines, are derived directly or indirectly from the tryptophan metabolism. This metabolic pathway is responsible for nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate, which participate in basic cellular processes.It was discovered some thirty years ago that kynurenines have neuroactive properties. Kynurenine, the central compound of this pathway, can be converted to two other important agents: the neuroprotective kynurenic acid and the neurotoxic quinolinic acid.Kynurenic acid is an endogenous broad-spectrum antagonist of excitatory amino acid receptors, including the N-methyl-D-aspartate receptors. It can inhibit the overexcitation of these receptors and reduce the cell damage induced by excitotoxins. Moreover, kynurenic acid non-competitively blocks the 7-nicotinic acetylcholine receptors, thereby permitting modulation of the cholinergic and glutamatergic neurotransmission.Quinolinic acid is a selective N-methyl-D-aspartate receptor agonist which can cause lipid peroxidation, the generation of free radicals and apoptosis via the overexcitation of these receptors.Changes in the relative or absolute concentrations of the kynurenines have been found in several neurodegenerative disorders, such as Huntington's disease and Parkinson's disease, stroke and epilepsy, in which the hyperactivation of amino acid receptors could be involved.Increase of the brain level of kynurenic acid seems to be a good therapeutic strategy; however, kynurenic acid can cross the blood-brain barrier only poorly. The latest findings provide promising opportunities involving the development of the analogues 4-chloro-kynurenine and glucoseamine-kynurenic acid, which can enter the brain and exert neuroprotective effects. Another recent possibility is the use of different enzyme inhibitors which can reduce the production of the neurotoxic quinolinic acid.The central compound of the KP is L-kynurenine (L-KYN), produced from TRP via a transition product, formyl-KYN, with the aid of TRP-or indoleamine-2,3-dioxygenase (TDO or IDO). Its cardinal role is to serve as the precursor of the neuroprotective kynurenic acid (KYNA) and the neurotoxic (QUIN).60% of L-KYN is taken up from the periphery, and the residual 40% is formed in the brain. The rate of cerebral KYN synthesis is 0.29 nmol/g/h [3]. It can readily cross the blood-brain barrier (BBB) with the aid of large neutral amino acid carriers [4].KYNA is formed directly from L-KYN by irreversible transamination. This process is catalysed by KYN aminotransferase (KAT), and in most brain regions by KAT II [5], which is located mainly in the glia [6].The glia has uptake mechanisms for KYN and the ability to release KYNA [7,8].KYNA, a broad-spectrum antagonist of the excitatory amino acid receptors, can act primarily at the strychnineinsensitive glycine-binding site of the N-methyl-D-aspartate (NMDA) receptors (IC 50 : ~8 M) [9]. Moreover, KYNA non-competitively blocks the 7-nicotinic acetylcholine (nACh) receptors ...

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Glial‐Neuronal Transfer of Arginine and S‐Nitrosothiols in Nitric Oxide Transmission

Cited by 21 publications

References 82 publications

Brain nitric oxide: Regional characterisation of a real-time microelectrochemical sensor

Brain nitric oxide: Regional characterisation of a real-time microelectrochemical sensor

Role of Kynurenines in the Central and Peripherial Nervous Systems

Neuromodulation of Hippocampal Synaptic Plasticity, Learning, and Memory by Noradrenaline

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