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Glutamate Receptor Agonists Stimulate Nitric Oxide Synthase in Primary Cultures of Cerebellar Granule Cells
Author(s) -
Kiedrowski Lech,
Costa Erminio,
Wroblewski Jarda T.
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb09315.x
Subject(s) - nmda receptor , kainate receptor , citrulline , glutamate receptor , chemistry , arginine , nitric oxide synthase , agonist , ampa receptor , biochemistry , stimulation , excitotoxicity , receptor , medicine , endocrinology , biology , enzyme , amino acid
The glutamate receptor agonist N ‐methyl‐D‐aspartate (NMDA) stimulated a rapid, extracellular Ca 2+ ‐dependent conversion of [ 3 H]arginine to [ 3 H]citrulline in primary cultures of cerebellar granule cells, indicating receptor‐mediated activation of nitric oxide (NO) synthase. The NMDA‐induced formation of [ 3 H]citrulline reached a plateau within 10 min. Subsequent addition of unlabeled l ‐arginine resulted in the disappearance of 3 H from the citrulline pool, indicating a persistent activation of NO synthase after NMDA receptor stimulation. Glutamate, NMDA, and kainate, but not quisqualate, stimulated both the conversion of [ 3 H]arginine to [ 3 H]citrulline and cyclic GMP accumulation in a dose‐dependent manner. Glutamate and NMDA showed similar potencies for the stimulation of [ 3 H]citrulline formation and cyclic GMP synthesis, respectively, whereas kainate was more potent at inducing cyclic GMP accumulation than at stimulating [ 3 H]citrulline formation. Both the [ 3 H]arginine to [ 3 H]citrulline conversion and cyclic GMP synthesis stimulated by NMDA were inhibited by the NMDA receptor antagonist MK‐801 and by the inhibitors of NO synthase, N G ‐monomethyl‐L‐arginine (MeArg) and N G ‐nitro‐L‐arginine (NOArg). However, MeArg, in contrast to NOArg, also potently inhibited [ 3 H]arginine uptake. Kainate (300 μ M ) stimulated 45 Ca 2+ influx to the same extent as 100 μ M NMDA, but stimulated [ 3 H]citrulline formation to a much lesser extent, which suggests that NO synthase is localized in subcellular compartments where the Ca 2+ concentration is regulated mainly by the NMDA receptor.