title: Cyclic GMP modulators and excitotoxic injury in cerebral cortical cultures.
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.
authors.affiliation: Department of Neurology, University of California, San Francisco 94110.
authors.forename: H S
authors.initials: HS
authors.lastname: Lustig
authors.forename: K L
authors.initials: KL
authors.lastname: von Brauchitsch
authors.forename: J
authors.initials: J
authors.lastname: Chan
authors.forename: D A
authors.initials: DA
authors.lastname: Greenberg
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology / Q000503:physiopathology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000098:blood supply* / Q000196:embryology / Q000201:enzymology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D007770:L-Lactate Dehydrogenase; D006152:Cyclic GMP