The Expression of NMDA Receptor Subunits in Cerebral Cortex and Hippocampus is Differentially Increased by Administration of Endobain E, a Na+, K+-ATPase Inhibitor

Ouabain exerts neurotoxic action and activates the population of NMDA receptors. Herein the effect of ouabain on the expression of NMDA subunits was evaluated. Adult Wistar rats were administered intracerebroventricularly with 0.1, 10 and 100 nmol ouabain or saline solution (control). Two days later, membranes of cerebral cortex and hippocampus were isolated. Western blots with antibodies for the NMDA receptor subunits: NR1; NR2A; NR2B; NR2C and NR2D were carried out. In cerebral cortex, NR2D subunit increased 30% with 10 nmol ouabain dose. With 100 nmol ouabain, NR1 and NR2D subunits enhanced 40 and 20%, respectively. In hippocampus, with the dose of 0.1 nmol ouabain, NR1 subunit enhanced roughly 50% whereas NR2B subunit decreased 30%. After administration of 10 nmol ouabain dose, NR2A, NR2B and NR2C subunits decreased 40, 50 and 30%, respectively. With the dose of 100 nmol of ouabain, NR1, NR2A and NR2B subunits diminished 10-20%. It is concluded that ouabain administration led to a differential regulation in the expression of NMDA subunits. These results may be correlated with the modulatory action of ouabain on NMDA receptor.

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“…, K ? -ATPase inhibitor, endobain E, differentially modifies the expression of glutamatergic ionotropic NMDA receptor subunits [52].…”

Section: Discussionmentioning

confidence: 99%

Intracerebroventricular Administration of Ouabain to Rats Changes the Expression of NMDA Receptor Subunits in Cerebral Cortex and Hippocampus

Bersier

Arnaiz

2009

Neurochem Res

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“…Taken jointly, findings indicated that ouabain and endogenous inhibitor endobain E differentially increased expression of NMDA receptor subunits [19,20] and that this effect was concomitant with changes in Na ? , K ?…”

Section: Discussionmentioning

confidence: 88%

“…-ATPase a3 subunit expression enhance in cerebral cortex and hippocampus and that the effect was dose-dependent. It is of interest to recall that the doses of endobain E employed herein (1 ll and 10 ll) are the same which proved effective to produce statistically significant increases in the expression of most NMDA subunits in cerebral cortex and hippocampus [19].…”

Section: Discussionmentioning

confidence: 97%

“…-ATPase inhibitors was analyzed. Both qualitative and quantitative alterations of NMDA receptor subunit expression were recorded [19,20].…”

Section: Discussionmentioning

confidence: 99%

“…The administration of endobain E and ouabain led to differential regulation of NMDA subunit expression [19,20]. Taken into account these findings, to learn about a potential interplay between the regulation of NMDA receptor and Na ?…”

Section: Introductionmentioning

confidence: 99%

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Changes in Na+, K+-ATPase Activity and Alpha 3 Subunit Expression in CNS After Administration of Na+, K+-ATPase Inhibitors

2010

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The expression of Na(+), K(+)-ATPase α3 subunit and synaptosomal membrane Na(+), K(+)-ATPase activity were analyzed after administration of ouabain and endobain E, respectively commercial and endogenous Na(+), K(+)-ATPase inhibitors. Wistar rats received intracerebroventricularly ouabain or endobain E dissolved in saline solution or Tris-HCl, respectively or the vehicles (controls). Two days later, animals were decapitated, cerebral cortex and hippocampus removed and crude and synaptosomal membrane fractions were isolated. Western blot analysis showed that Na(+), K(+)-ATPase α3 subunit expression increased roughly 40% after administration of 10 or 100 nmoles ouabain in cerebral cortex but remained unaltered in hippocampus. After administration of 10 μl endobain E (1 μl = 28 mg tissue) Na(+), K(+)-ATPase α3 subunit enhanced 130% in cerebral cortex and 103% in hippocampus. The activity of Na(+), K(+)-ATPase in cortical synaptosomal membranes diminished or increased after administration of ouabain or endobain E, respectively. It is concluded that Na(+), K(+)-ATPase inhibitors modify differentially the expression of Na(+), K(+)-ATPase α3 subunit and enzyme activity, most likely involving compensatory mechanisms.

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Different neuronal Na⁺/K⁺‐ATPase isoforms are involved in diverse signaling pathways

Karpova

Bulygina

Boldyrev

2010

Cell Biochemistry & Function

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Inhibition of rat neuronal Na(+)/K(+)-ATPase alpha3 isoform at low (100 nM) ouabain concentration led to activation of MAP kinase cascade via PKC and PIP(3) kinase. In contrast to ouabain-sensitive alpha3 isoform of Na(+)/K(+)-ATPase, an ouabain-resistant alpha1 isoform (inhibition with 1 mM of ouabain) of Na(+)/K(+)-ATPase regulates MAP kinase via Src kinase dependent reactions. Using of Annexin V-FITC apoptotic test to determine the cells with early apoptotic features allows to conclude that alpha3 isoform stimulates and alpha1 suppresses apoptotic process in cerebellum neurons. These data are the first demonstration showing participation of ouabain-resistant (alpha1) and ouabain-sensitive (alpha3) Na(+)/K(+)-ATPase isoforms in diverse signaling pathways in neuronal cells.

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The Expression of NMDA Receptor Subunits in Cerebral Cortex and Hippocampus is Differentially Increased by Administration of Endobain E, a Na+, K+-ATPase Inhibitor

Cited by 16 publications

References 47 publications

Intracerebroventricular Administration of Ouabain to Rats Changes the Expression of NMDA Receptor Subunits in Cerebral Cortex and Hippocampus

Intracerebroventricular Administration of Ouabain to Rats Changes the Expression of NMDA Receptor Subunits in Cerebral Cortex and Hippocampus

Changes in Na+, K+-ATPase Activity and Alpha 3 Subunit Expression in CNS After Administration of Na+, K+-ATPase Inhibitors

Different neuronal Na⁺/K⁺‐ATPase isoforms are involved in diverse signaling pathways

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The Expression of NMDA Receptor Subunits in Cerebral Cortex and Hippocampus is Differentially Increased by Administration of Endobain E, a Na+, K+-ATPase Inhibitor

Cited by 16 publications

References 47 publications

Intracerebroventricular Administration of Ouabain to Rats Changes the Expression of NMDA Receptor Subunits in Cerebral Cortex and Hippocampus

Intracerebroventricular Administration of Ouabain to Rats Changes the Expression of NMDA Receptor Subunits in Cerebral Cortex and Hippocampus

Changes in Na+, K+-ATPase Activity and Alpha 3 Subunit Expression in CNS After Administration of Na+, K+-ATPase Inhibitors

Different neuronal Na+/K+‐ATPase isoforms are involved in diverse signaling pathways

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Product

Resources

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Different neuronal Na⁺/K⁺‐ATPase isoforms are involved in diverse signaling pathways