Activation of nitric oxide pathway mediated by metabotropic glutamate receptors in primary cultures of cerebellar granule cells |
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Authors: | N V Gorbunov |
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Institution: | (1) I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg;(2) Instituto di Ricerche Farmacologiche “Mario Negri”, Consorzio “Mario Negri” Sud, Italy |
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Abstract: | Stimulation of L-glutamate receptors (GluRs) is thought to produce neuron death through the elevation of free intracellular
Ca2+ levels, leading to activation of Ca2+/calmodulin-dependent synthesis of cytotoxic amounts of NO·. In the present study, NO synthase activation mediated by mGluR
stimulation is investigated in primary cultures of granule cells (CGrC). It is found that a selective agonist of mGluRs, DL-1-aminocyclopentane-trans-1,3-dicarboxylic
acid (ACPD), raises both the cGMP and nitrite (NO2
−) levels, which are used as a biochemical index to study the enzymatic NO· release from L-arginine. This effect is abolished
by applying both Nω-nitro-L-arginine methyl ester (NAME) and DL-2-amino-4-phosphonobytyric acid (AP4), and is independent
of Ca2+. In contrast, the α-amino-3-hydroxy-5-methylisoxarole-4-propionnate (AMPA)-induced increase in cGMP content is eliminated
by the preincubation of CGrC with 4 mM EGTA-chelated Ca2+.
Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N
o
7, pp. 46–49, July, 1995
Presented by Yu. A. Romanov, Member of the Russian Academy of Medical Sciences |
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Keywords: | nitric oxide L-glutamate receptor granule cells cerebellum |
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