In vitro studies of the influence of glutamatergic agonists on the Na+,K+-ATPase and K+-p-nitrophenylphosphatase activities in the hippocampus and frontal cortex of rats

Journal of Negative Results in Biomedicine

Marcos Brandão Contó¹ 

[1] Departamento de Psicobiologia, Universidade Federal de São Paulo, Escola Paulista de Medicina (UNIFESP/EPM), Rua Botucatu 862, 1° andar, Vila Clementino, São Paulo, SP, 04023-062, Brazil

关键词: Hippocampus;    Frontal cortex;    Kainate;    NMDA;    AMPA;    Glutamate;    K⁺-p-nitrophenylphosphatase;    Na⁺,K⁺-ATPase;   

Others  :  815301
DOI  :  10.1186/1477-5751-11-12

 received in 2012-01-17, accepted in 2012-04-24,  发布年份 2012

【 摘 要 】

Background

The overstimulation of excitatory glutamatergic neurotransmission and the inhibition of Na⁺,K⁺-ATPase enzymatic activity have both been implicated in neurotoxicity and are possibly related to the pathogenesis of epilepsy and neurodegenerative disorders. In the present study, we investigated whether glutamatergic stimulation by the glutamatergic agonists glutamate, α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDA) modulates the Na⁺,K⁺-ATPase and the K⁺-p-nitrophenylphosphatase activities in the crude synaptosomal fraction of the hippocampus and the frontal cortex of rats.

Results

Our results demonstrated that these glutamatergic agonists did not influence the activities of Na⁺,K⁺-ATPase or K⁺-p-nitrophenylphosphatase in the brain structures analyzed. Assays with lower concentrations of ATP to analyze the preferential activity of the Na⁺,K⁺-ATPase isoform with high affinity for ATP did not show any influence either.

Conclusions

These findings suggest that under our experimental conditions, the stimulation of glutamatergic receptors does not influence the kinetics of the Na⁺,K⁺-ATPase enzyme in the hippocampus and frontal cortex.

【 授权许可】

   
2012 Contó and Venditti.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Meldrum BS: Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nut 2000, 130:1007S-1015S.
• [2]Camacho A, Massieu L: Role of glutamate transporters in the clearance and release of glutamate during ischemia and its relation to neuronal death. Arch Med Res 2006, 37:11-18.
• [3]Li S, Stys PK: Na+K+ -ATPase inhibition and depolarization induce glutamate release via reverse Na+-dependent transport in spinal cord of white matter. Neurosc 2001, 107(4):675-683.
• [4]Rose AM, Valdes R: Understanding the sodium pump and its relevance to disease. Clin Chem 1994, 40(9):1674-1685.
• [5]Therien A, Blostein R: Mechanisms of sodium pump regulation. Am J Physiol Cell Physiol 2000, 279:C541-C566.
• [6]Yu SP: Na+, K+-ATPase: the new face of an old player in pathogenesis and apoptotic/hybrid cell death. Biochem Pharmacol 2003, 66:1601-1609.
• [7]Mobasheri A, Avila J, Cózar-Castellano I, Brownleader MD, Trevan M, Francis MJO, Lamb JF, Martin-Vasallo P: Na+, K+-ATPase isozyme diversity; comparative biochemistry and physiological implications of novel functional interactions. Biosci Rep 2002, 20(2):51-91.
• [8]Blanco G, Mercer RW: Isozymes of the Na-K-ATPase: heterogeneity in structure, diversity in function. Am J Physiol 1998, 275:F633-F650.
• [9]Jewell EA, Lingrel JB: Comparison of the substrate dependence properties of the rat Na, K-ATPase α1, α2 and α3 isoforms expressed in HeLa Cells. J Biol Chem 1991, 266(25):16925-16930.
• [10]Bignami A, Palladini G: Experimentally produced cerebral status spongiosus and continuous pseudorhythmic electroencephalographic discharges with a membrane-ATPase inhibitor in the rat. Nature 1966, 209:413-414.
• [11]Pedley TA, Zuckermann EC, Glaser GH: Epileptogenic effects of localized ventricular perfusion of ouabain on dorsal hippocampus. Exp Neurol 1969, 25:207-219.
• [12]Inoue N, Soga T, Kato T: Glutamate receptors mediate regulation of Na pump isoform activities in neurons. Neuroreport 1999, 10:3289-3293.
• [13]Marcaida G, Kosenko E, Miñana M-D, Grisolía S, Felipo V: Glutamate induces a calcineurin-mediated dephosphorylation of Na+, K+-ATPase that results in its activation in cerebellar neurons in culture. J Neurochem 1996, 66(1):99-104.
• [14]Pellerin L, Magistretti PJ: Glutamate uptake stimulates Na+, K+−ATPase activity in astrocytes via activation of a distinct subunit highly sensitive to ouabain. J Neurochem 1997, 69(5):2132-2137.
• [15]Avrova NF, Victorov IV, Tyurin VA, Zakharova IO, Sokolova TV, Andreeva NA, et al.: Inhibition of glutamate-induced intensification of free radical reactions by gangliosides: possible role in their protective effect in rat cerebellar granule cells and brain synaptosomes. Neurochem Res 1998, 23(7):945-952.
• [16]Boldyrev A, Bulygina E, Carpenter D, Schoner W: Glutamate receptors communicate with Na+, K+-ATPase in rat cerebellum granule cells. J Mol Neurosci 2003, 21:213-222.
• [17]Bulygina ER, Yu L, Boldyrev AA: Activation of glutamate receptors inhibits Na/K-ATPase of cerebellum granule cells. Biochem (Moscow) 2002, 67(9):1001-1005.
• [18]Bulygina E, Gerasimova O, Boldyrev A: Glutamate receptors regulate Na/K-ATPase in cerebellum neurons. Ann NY Acad Sci 2003, 986:611-613.
• [19]Nanitsos EK, Acosta GB, Saihara Y, Stanton D, Liao LP, Shin JW, Rae C, Balcar VJ: Effects of glutamate transport substrates and glutamate receptor ligands on the activity of Na+/K+-ATPase in brain tissue in vitro. Clin Exp Pharmacol Physiol 2004, 31:762-769.
• [20]Desaiah D, Ho IK: Kinetics of catecholamine sensitive Na+-K+ ATPase activity in mouse brain synaptosomes. Biochem Pharmacol 1977, 26:2029-2035.
• [21]de Rodríguez Lores Arnaiz G, de Antonelli Gómez Lima M: The effect of several neurotransmitter substances on nerve ending membrane ATPase. Acta Physiol Latinoam 1981, 6:43-48.
• [22]Cousin MA, Nicholls DG, Pocock JM: Modulation of ion gradients and glutamate release in cultured cerebellar granule cells by ouabain. J Neurochem 1995, 64(5):2097-2104.
• [23]Veldhuis W, van der Stelt M, Delmas F, Gillet B, Veldink GA, Vliegenthart JFG, Nicolay K, Bär PR: In vivo excitotoxicity induced by ouabain, a Na+/K+-ATPase inhibitor. J Cereb Blood Flow Metab 2003, 23:62-74.
• [24]Dale N, Frenguelli BG: Release of adenosine and ATP during ischemia and epilepsy. Curr Neuropharmacol 2009, 7:160-179.
• [25]Tsuji K, Nakamura Y, Ogata T, Shibata T, Kataoka K: Rapid decrease in ATP content without recovery phase during glutamate-induced cell death in cultured spinal neurons. Brain Res 1994, 662:289-292.
• [26]Alves R, de Carvalho JGB, Benedito MAC: High and low rearing subgroups of rats selected in the open Field differ in the activity of K+-stimulated-p-nitrophenylphosphatase in the hippocampus. Brain Res 2005, 1058:178-182.
• [27]Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 1951, 193:265-275.
• [28]Albers RW, de Rodrigues Lores Arnaiz G, De Robertis E: Sodium-potassium-activated ATPase and potassium-activated p-nitrophenyl-phosphatase: a comparison of their subcellular localization in rat brain. Proc Natl Acad Sci USA 1965, 53:557-564.
• [29]Lowry OH, Lopez JA: The determination of inorganic phosphate in the presence of labile phosphate esters. J Biol Chem 1946, 162:421-428.