The effects of NMDA receptor antagonists over intestinal ischemia/reperfusion injury in rats

Cámara-Lemarroy, Carlos R.; Garza, Francisco Javier Guzmán-de la; Alarcón-Galván, Gabriela; Cordero-Pérez, Paula; Fernández-Garza, Nancy Esthela

doi:10.1016/j.ejphar.2009.08.038

Cited by 30 publications

(20 citation statements)

References 62 publications

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“…Exposure of isolated myenteric ganglia to high extracellular concentrations of glutamate, mimicking ischemic conditions, induces neuronal death, mainly via NMDA and AMPA/kainate receptor activation [17]. There are studies suggesting that glutamate receptors of the NMDA type may participate to alterations of enteric neurotransmitter pathways after I/R injury leading to gastrointestinal dismotility [10], [11], [18]. In the present study, to further investigate the mechanisms underlying glutamate-mediated neurotoxicity in myenteric neurons following an I/R insult, we evaluated whether ionotropic glutamate receptors of the NMDA and AMPA/kainate type are involved in myenteric neuron cell damage induced by I/R.…”

Section: Introductionmentioning

confidence: 99%

Antagonism of Ionotropic Glutamate Receptors Attenuates Chemical Ischemia-Induced Injury in Rat Primary Cultured Myenteric Ganglia

et al. 2014

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Alterations of the enteric glutamatergic transmission may underlay changes in the function of myenteric neurons following intestinal ischemia and reperfusion (I/R) contributing to impairment of gastrointestinal motility occurring in these pathological conditions. The aim of the present study was to evaluate whether glutamate receptors of the NMDA and AMPA/kainate type are involved in myenteric neuron cell damage induced by I/R. Primary cultured rat myenteric ganglia were exposed to sodium azide and glucose deprivation (in vitro chemical ischemia). After 6 days of culture, immunoreactivity for NMDA, AMPA and kainate receptors subunits, GluN1 and GluA1–4, GluK1–3 respectively, was found in myenteric neurons. In myenteric cultured ganglia, in normal metabolic conditions, -AP5, an NMDA antagonist, decreased myenteric neuron number and viability, determined by calcein AM/ethidium homodimer-1 assay, and increased reactive oxygen species (ROS) levels, measured with hydroxyphenyl fluorescein. CNQX, an AMPA/kainate antagonist exerted an opposite action on the same parameters. The total number and viability of myenteric neurons significantly decreased after I/R. In these conditions, the number of neurons staining for GluN1 and GluA1–4 subunits remained unchanged, while, the number of GluK1–3-immunopositive neurons increased. After I/R, -AP5 and CNQX, concentration-dependently increased myenteric neuron number and significantly increased the number of living neurons. Both -AP5 and CNQX (100–500 µM) decreased I/R-induced increase of ROS levels in myenteric ganglia. On the whole, the present data provide evidence that, under normal metabolic conditions, the enteric glutamatergic system exerts a dualistic effect on cultured myenteric ganglia, either by improving or reducing neuron survival via NMDA or AMPA/kainate receptor activation, respectively. However, blockade of both receptor pathways may exert a protective role on myenteric neurons following and I/R damage. The neuroprotective effect may depend, at least in part, on the ability of both receptors to increase intraneuronal ROS production.

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Section: Introductionmentioning

confidence: 99%

Antagonism of Ionotropic Glutamate Receptors Attenuates Chemical Ischemia-Induced Injury in Rat Primary Cultured Myenteric Ganglia

et al. 2014

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“…Glutamate represents another well known player in the scenario of neuronal damage following I/R (Lau and Tymianski, 2010). In the gut after I/R injury, a surge of the amino acid overflow induces a sustained activation of ionotropic NMDA (N-methyl-D-aspartate) receptors, which are abundantly expressed in myenteric neurons (Kirchgessner, 2001;Giaroni et al, 2003), and participates to the neuronal alterations underlying gastrointestinal dismotility (Calcina et al, 2005;Giuliani et al, 2006;Cámara-Lemarroy et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Interaction between NMDA glutamatergic and nitrergic enteric pathways during in vitro ischemia and reperfusion

Filpa

Carpanese

Marchet

et al. 2015

European Journal of Pharmacology

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“…It is known that NMDA receptors exist in the enteric nervous system and NMDA antagonists are effective in reducing the functional alterations associated with intestinal I/R [20]. In previous studies, we have also demonstrated that ketamine, an NMDA antagonist, could reduce intestinal I/R injury, although whether this was due to NMDA-related effects, or to ketamine's antiinflammatory activity, remains unclear [10, 19, 21].…”

Section: Discussionmentioning

confidence: 94%

Comparative Effects of Triflusal, S-Adenosylmethionine, and Dextromethorphan over Intestinal Ischemia/Reperfusion Injury

Cámara-Lemarroy

Garza

Cordero-Pérez

et al. 2011

The Scientific World JOURNAL

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Ischemia/reperfusion (I/R) is a condition that stimulates an intense inflammatory response. No ideal treatment exists. Triflusal is an antiplatelet salicylate derivative with anti-inflammatory effects. S-adenosylmethionine is a metabolic precursor for glutathione, an endogenous antioxidant. Dextromethorphan is a low-affinity N-methyl-D-aspartate receptor inhibitor. There is evidence that these agents modulate some of the pathways involved in I/R physiopathology. Intestinal I/R was induced in rats by clamping the superior mesenteric artery for 60 minutes, followed by 60 minutes of reperfusion. Rats either received saline or the drugs studied. At the end of the procedure, serum concentrations of tumor necrosis factor-alpha (TNF-alpha), malonaldehyde (MDA), and total antioxidant capacity (TAC) were determined and intestinal morphology analyzed. I/R resulted in tissue damage, serum TNF-alpha and MDA elevations, and depletion of TAC. All drugs showed tissue protection. Only triflusal reduced TNF-alpha levels. All drugs lowered MDA levels, but only triflusal and S-adenosylmethionine maintained the serum TAC.

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The effects of NMDA receptor antagonists over intestinal ischemia/reperfusion injury in rats

Cited by 30 publications

References 62 publications

Antagonism of Ionotropic Glutamate Receptors Attenuates Chemical Ischemia-Induced Injury in Rat Primary Cultured Myenteric Ganglia

Antagonism of Ionotropic Glutamate Receptors Attenuates Chemical Ischemia-Induced Injury in Rat Primary Cultured Myenteric Ganglia

Interaction between NMDA glutamatergic and nitrergic enteric pathways during in vitro ischemia and reperfusion

Comparative Effects of Triflusal, S-Adenosylmethionine, and Dextromethorphan over Intestinal Ischemia/Reperfusion Injury

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