Nitric oxide (NO) release by glutamate and NMDA in the dorsal horn of the spinal cord: an in vivo electrochemical approach in the rat

Rivot, J.P.; Sousa, Ângela Maria; Montagne-Clavel, Jacqueline; Besson, Jean‐Marie

doi:10.1016/s0006-8993(99)01075-6

Cited by 35 publications

(18 citation statements)

References 61 publications

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“…Finally, although interference by high dopamine concentrations is possible [17], we did not find evidence for changes in NO electrochemical detection at both extremes of oxygen concentration within the calibration solutions. The present data further concur with a recent report by Rivot et al [21] who showed that continuous NO production occurs within the nervous tissue, is enhanced by NMDA, and can be modified by NOS inhibitors and NO donors. Similarly, using the calibration curve obtained from in vitro experiments, the mean amplitude of the oxidation current generated during basal conditions within the tissue would correspond to F0.15 ÌM in the young pups and F0.4-0.5 ÌM in the adult rat, the latter values being strikingly similar to those previously reported in the rat [18].…”

Section: Discussionsupporting

confidence: 93%

Brainstem Nitric Oxide Tissue Levels Correlate with Anoxia-Induced Gasping Activity in the Developing Rat

Gozal

Torres²

2001

Neonatology

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Gasping is an important mechanism for survival that appears to be developmentally modulated by the glutamate-nitric oxide (NO) pathway. However, the temporal characteristics of NO brain tissue levels during gasping are unknown. We hypothesized that during anoxia-induced gasping, the gasping frequency would be closely correlated with caudal brainstem tissue NO concentrations in developing rats. Brainstem and cortical tissue NO levels were measured during anoxia using a voltammetric electrode in adult rats and 5-day-old pups during control conditions and following pretreatment with the NMDA receptor antagonist MK-801 (1 mg/kg) or the neuronal NO synthase inhibitor 7-nitro-indazole (7-NI; 100 mg/kg). In young animals, NO tissue levels followed a triphasic trajectory coincident with gasp frequency which was markedly altered by MK-801 and 7-NI, albeit with preservation of gasp frequency-NO tissue level relationships. In adult rats, 40-fold higher NO tissue levels occurred and followed a monophasic trajectory coincident with gasp patterning. In the cortex, monophasic increases in NO levels occurred at all ages. We conclude that anoxia-induced gasping neurogenesis is modulated via NMDA-NO mechanisms in the developing rat. We postulate that higher NO brainstem concentrations may favor early autoresuscitation, but limit anoxic tolerance.

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Section: Discussionsupporting

confidence: 93%

Brainstem Nitric Oxide Tissue Levels Correlate with Anoxia-Induced Gasping Activity in the Developing Rat

Gozal

Torres²

2001

Neonatology

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“…Indeed, the NMDA receptor complex is physically coupled to the Ca 2ϩ -activated enzyme neuronal NOS (Sheng and Pak, 2000), and several reports have shown an accumulation of nitrites in the extracellular matrix in vivo after NMDA treatment (Luo et al, 1993;Kendrick et al, 1996;Meyer et al, 1998;Rivot et al, 1999). Concentration-response analysis for the NMDA effect gave an EC 50 of 48 M (Fig.…”

Section: Discussionmentioning

confidence: 92%

“…Indeed, the accumulation of nitrites as assessed by microdialysis occurs over minutes or tens of minutes (Luo et al, 1993;Meyer et al, 1998;Rivot et al, 1999). Because of their larger size and polarity, NMDA molecules diffuse slower from the site of application than NO ⅐ , a process expected to increase the number of NO ⅐ sources and cause more prolonged generation of NO ⅐ .…”

Section: Discussionmentioning

confidence: 99%

“…However, in previous voltammetry studies aimed at measuring NO ⅐ (Malinski and Taha, 1992;Rivot et al, 1999), the oxidation of accumulated nitrites could have contributed substantially to the measured NO ⅐ signal, as suggested by more recent studies (Crespi et al, 2001). Clearly, measuring the accumulation of stable metabolites may preclude the detection of changes of NO ⅐ release in response to dynamic modifications of excitatory transmission or NMDA receptor function.…”

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confidence: 98%

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Pulse of Nitric Oxide Release in Response to Activation ofN-Methyl-d-aspartate Receptors in the Rat Striatum: Rapid Desensitization, Inhibition by Receptor Antagonists, and Potentiation by Glycine

Crespi¹,

Rossetti²

2004

J Pharmacol Exp Ther

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Increased activity of glutamate N-methyl-D-aspartate (NMDA) receptors is the dominant mechanism by which nitric oxide (NO ⅐ ) is generated. By using a selective direct-current amperometry method, we characterized real time NO ⅐ release in vivo in response to chemical stimulation of NMDA receptors in the rat striatum. The application of NMDA caused the appearance of a sharp and transient oxidation signal. Concentration-response studies (10 -500 M) indicated an EC 50 of 48 M. The NMDA-induced amperometric signal was suppressed by focal application of the nitric-oxide synthase inhibitor L-nitro-arginine methyl ester (L-NAME, 100 M) or D-(Ϫ)-2-amino-5-phosphonopentanoic acid (AP-5, 100 M) or by systemic injection of dizocilpine (1 mg/kg i.p.), drugs that, when given alone, had no effect on baseline oxidation current. Repeated injections of NMDA at short intervals (ϳ80 s) resulted in a progressive reduction of the amperometric signal with a decay half-life of 1.36 min. Sixty min after the last NMDA application the amperometric response was restored to initial levels. Finally, the coapplication of glycine (50 or 100 M), which, when given alone had no effect, potentiated the NMDA-induced response. Thus, NMDA receptor-mediated activation of striatal NO ⅐ system shuts off quickly and undergoes rapid desensitization, suggesting a feedback inhibition of NMDA receptor function. To the extent of NO ⅐ release can represent a correlate of NMDA receptor activity, its amperometric detection could be useful to assess in vivo the state of excitatory transmission under physiological, pharmacological, or pathological conditions. Nitric oxide (nitrogen monoxide, NO ⅐ ) is a free radical species that is released in the brain in response to neuronal depolarization. NO ⅐ is a small, lypophylic molecule that readily diffuses between and within cells. As such, it can act distally of the cellular site of production, but it rapidly decays due to its short half-life (0.2-120 s; Kelm et al., 1988;Moncada et al., 1989;Ford et al., 1993;Wood and Garthwaite, 1994;Crespi et al., 2001). In the brain NO ⅐ is implicated, among other things, in neurotransmitter release, learning and memory, neuronal plasticity, and gene expression and neuronal degeneration and survival (Snyder, 1992;Bruhwyler et al., 1993;Schuman and Madison, 1994). Although several pathways that cause nonspecific depolarizations and elevations of intracellular Ca 2ϩ can stimulate NO ⅐ formation, increased activity of glutamate N-methyl-D-aspartate (NMDA) receptor represents the dominant mechanism by which NO ⅐ is generated in the brain (Garthwaite and Garthwaite, 1987;Garthwaite and Boulton, 1995). Indeed, the NMDA receptor complex is physically coupled (Sheng and Pak, 2000) to nitric-oxide-synthase (NOS; EC 1.14.13.39), a Ca 2ϩ -calmodulin-sensitive, protein kinase C-dependent enzyme that catalyzes the formation of NO ⅐ from L-arginine. Therefore, NO ⅐ formation and release can be considered a neurochemical correlate of the functional activation of NMDA receptor-mediated...

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“…The NR1 subunit is a key component of NR1-3 heteromeric NMDA receptors and is believed to be part of the composition of native NMDA receptors (Sugihara et al, 1992;Ishii et al, 1993;Hollmann and Heinemann, 1994;Laurie et al, 1995;Mori and Mishina, 1995). Previous studies, using electrophysiological and pharmacological approaches to demonstrate a role of NMDA receptors in synaptic transmission in the dorsal horn, have generally provided only indirect evidence for the site of action of excitatory amino acids (Davies and Lodge, 1987;Dickenson and Sullivan, 1987;Dougherty and Willis, 1992;Nagy et al, 1993;Rivot et al, 1999) (cf. Bardoni et al, 1998); therefore, it is often uncertain whether the NMDA receptors targeted by the drug are on the neuron from which recordings are being made or on primary afferent (Liu et al, 1994) or interneuronal terminals.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Phosphorylation of NMDA Receptor 1 Subunits in Spinal Cord Dorsal Horn and Spinothalamic Tract Neurons after Intradermal Injection of Capsaicin in Rats

2000

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The functional enhancement of NMDA receptors after peripheral tissue injury is proposed to contribute to the sensitization of spinothalamic tract (STT) cells and hyperalgesia. Protein phosphorylation is a major mechanism for the regulation of NMDA receptor function. In this study, Western blots, immunofluorescence double labeling, and the retrograde tracing method were used to examine whether phosphorylation of NMDA receptor 1 (NR1) subunits increases in spinal cord tissue and spinal dorsal horn neurons, especially in STT cells, after injection of capsaicin (CAP) into the glabrous skin of one hindpaw of anesthetized rats. Western blots showed that phosphorylated NR1 protein in spinal cord tissue was increased 30 min after CAP injection. Immunofluorescence double-labeling staining showed no significant difference in the number of the NR1-like immunoreactive neurons in laminae I-VII in the lumbosacral segments (L 4 -S 1 ) on the ipsilateral and the contralateral sides 30 min after CAP or vehicle injection. However, the numbers of phospho-NR1-like immunoreactive neurons were significantly increased on the ipsilateral side compared with the vehicle injection group. STT cells were labeled by bilateral microinjections of the retrograde tracer fluorogold into the lateral thalamus, including the ventral-posterior lateral nucleus. Immunofluorescence staining was performed at 30, 60, and 120 min after CAP injection or at 30 min after vehicle injection. There was a significant increase in the proportion of STT cells with phosphorylated NR1 subunits compared either with the contralateral side 30 and 60 min after CAP injection or either side of animals after intradermal injection of vehicle. These results provide direct evidence that NMDA receptors in STT cells are phosphorylated after CAP injection. Key words: NMDA receptor subunit; phosphorylation; STT cell; retrograde tracing; dorsal horn; nociceptionSpinothalamic tract (STT) cells transmit nociceptive information from the spinal cord to the thalamus (Willis, 1985;Gybels and Sweet 1989;Willis and Coggeshall, 1991). Extracellular glutamate and aspartate concentrations increase significantly in the spinal cord dorsal horn after peripheral inflammation (Sluka and Westlund, 1992, 1993a;Sorkin et al., 1992;Sorkin and McAdoo, 1993;Sluka and Willis, 1998), and this increase is believed to underlie hyperalgesia and allodynia (Sluka and Westlund, 1993b) by enhancing the excitability of nociceptive dorsal horn neurons, including STT cells (Aanonsen et al., 1990; Willis, 1991, 1992; Dougherty et al., 1992a,b). Intrathecal administration of glutamate agonists such as NMDA elicits nociceptive behavior (Aanonsen and Wilcox, 1987), and spinal cord administration of an NMDA receptor antagonist attenuates hyperalgesia and allodynia (Haley et al., 1990; Ren et al., 1992a,b;Ren and Dubner, 1993;Sluka et al., 1994). At a cellular level, central sensitization of STT cells can be initiated by iontophoretic co-release of NMDA and substance P (cf. Randic et al., 1990;Dougherty and Willis, 1991...

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Nitric oxide (NO) release by glutamate and NMDA in the dorsal horn of the spinal cord: an in vivo electrochemical approach in the rat

Cited by 35 publications

References 61 publications

Brainstem Nitric Oxide Tissue Levels Correlate with Anoxia-Induced Gasping Activity in the Developing Rat

Brainstem Nitric Oxide Tissue Levels Correlate with Anoxia-Induced Gasping Activity in the Developing Rat

Pulse of Nitric Oxide Release in Response to Activation ofN-Methyl-d-aspartate Receptors in the Rat Striatum: Rapid Desensitization, Inhibition by Receptor Antagonists, and Potentiation by Glycine

Enhanced Phosphorylation of NMDA Receptor 1 Subunits in Spinal Cord Dorsal Horn and Spinothalamic Tract Neurons after Intradermal Injection of Capsaicin in Rats

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