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Glutamate modulates sodium‐potassium‐ATPase through cyclic GMP and cyclic GMP‐dependent protein kinase in rat striatum
Author(s) -
Munhoz Carolina Demarchi,
Kawamoto Elisa Mitiko,
de Sá Lima Larissa,
Lepsch Lucilia Brochado,
Glezer Isaias,
Marcourakis Tania,
Scavone Cristoforo
Publication year - 2004
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.1217
Subject(s) - cyclic gmp , potassium , chemistry , striatum , sodium , protein kinase a , atpase , biochemistry , glutamate receptor , biophysics , microbiology and biotechnology , phosphorylation , enzyme , biology , endocrinology , receptor , dopamine , organic chemistry
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 μ M ) and S‐nitroso‐N‐acetylpenicillamine (SNAP at 200 μ M ) increased α 2,3 Na + 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 μ M ) and 8‐Br‐cyclic GMP (4 m M ). 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 α 2,3 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 α 2,3 Na + K + ‐ATPase activity. Copyright © 2004 John Wiley & Sons, Ltd.