Cyclic GMP modulators and excitotoxic injury in cerebral cortical cultures |
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Authors: | Heather S. Lustig Kristine L. von Brauchitsch Jane Chan David A. Greenberg |
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Affiliation: | Department of Neurology, University of California, San Francisco 94110. |
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Abstract: | N-Methyl-D-aspartate (NMDA) receptor activation generates nitric oxide (NO) and cyclic GMP (cGMP) and produces 'excitotoxic' neuronal injury. To examine the possible role of cGMP in excitotoxicity, we evaluated the effects of agents that stimulate or inhibit cGMP activity on the release of lactate dehydrogenase from neuron-enriched cortical cultures. cGMP analogs exhibited no toxicity, and inhibitors of guanylate cyclase or of cGMP-dependent enzymes failed to protect cultures from the toxic effects of NMDA or the NO donor sodium nitroprusside. These findings argue against a role for cGMP in the pathogenesis of excitotoxic neuronal injury. |
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Keywords: | Cyclic GMP Excitotoxicity Cell culture N-Methyl-d-aspartate Sodium nitroprusside Guanylate cyclase Protein kinase Phosphodiesterase |
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