title: Glutamate modulates sodium-potassium-ATPase through cyclic GMP and cyclic GMP-dependent protein kinase in rat striatum.
abstract: Excessive excitatory action of glutamate and nitric oxide (NO) has been implicated in degeneration of striatal neurons. Evidence had been provided that Na+K+-ATPase might be involved in this process. Here we investigated whether glutamate-regulated messengers, such as NO and cyclic GMP, could modulate the activity of membrane Na+K+-ATPase. Our results demonstrated that NO donors sodium nitroprusside (SNP at 30 and 300 microM) and S-nitroso-N-acetylpenicillamine (SNAP at 200 microM) increased alpha2,3Na+K+-ATPase activity which was blocked by the NO chelator, haemoglobin and was independent of [Na+]. This regulation was associated with cGMP synthesis and mimicked by glutamate (300 microM) and 8-Br-cyclic GMP (4 mM). 8-Br-cGMP-induced stimulation of Na+K+-ATPase activity could be blocked by KT5823 (an inhibitor of cGMP-dependent protein kinase, PKG), but not by KT5720 (an inhibitor of cAMP-dependent protein kinase, PKA). N-Methyl-D-aspartate (NMDA) receptors appeared to be involved in the effect of glutamate, since MK-801 (NMDA receptor antagonist) produced a partial reduction in glutamate-induced activation of the enzyme. MK-801 was not synergistic to L-NAME (NOS inhibitor), suggesting that glutamate stimulates the NMDA-NOS pathway to activate alpha2,3 Na+K+-ATPase in rat striatum. This regulation was associated with cyclic GMP (but not cyclic AMP) synthesis. These data indicate the existence, in vitro, of a regulatory pathway by which glutamate, acting through NO and cGMP, can cause alterations in striatal alpha2,3 Na+K+-ATPase activity.
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Carolina Demarchi
authors.initials: CD
authors.lastname: Munhoz
authors.forename: Elisa Mitiko
authors.initials: EM
authors.lastname: Kawamoto
authors.forename: Larissa
authors.initials: L
authors.lastname: de Sá Lima
authors.forename: Lucilia Brochado
authors.initials: LB
authors.lastname: Lepsch
authors.forename: Isaias
authors.initials: I
authors.lastname: Glezer
authors.forename: Tania
authors.initials: T
authors.lastname: Marcourakis
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Scavone
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018698:Glutamic Acid / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D009599:Nitroprusside; D009569:Nitric Oxide; D018698:Glutamic Acid; D026423:S-Nitroso-N-Acetylpenicillamine; D000242:Cyclic AMP; D017869:Cyclic GMP-Dependent Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP