Regulation of nitric oxide synthase activity in cortical slices by excitatory amino acids and calcium

S. Alagarsamy, G. Lonart, K. M. Johnson

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Abstract

Nitric oxide synthase (NOS) activity was determined in adult rat frontal cortex and hippocampus by measuring the conversion of L-[3H]arginine to L- [3H]citrulline. N-methyl-D-aspartate (NMDA), but not kainate or α-amino-3- hydroxy-5-methylisoxazole-4-propionate (AMPA), stimulated NOS activity. This effect was concentration dependent (EC50 ≃ 30 μM) and was inhibited by tetrodotoxin, EGTA, N(ω)-nitro-L-arginine (NOARG), Mg2+, phencyclidine, and (cis)-4-phosphonomethyl-2-piperidine carboxylate (CGS 19755), but not by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). NOS activity was increased to an even greater extent by the calcium ionophores ionomycin and A23187 and by depolarization with 50 mM K+. Interestingly, neither caffeine nor 1- aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), drugs that would be expected to increase intracellular Ca2+ concentration by release of Ca2+ from intracellular ryanodine- and inositol-1,4,5-trisphosphate-sensitive stores, respectively, had any significant effect on NOS activity. It is concluded that NOS can be activated by NMDA binding to a classic NMDA glutamate receptor subtype as well as by depolarization or other agents that increase the influx of extracellular Ca2+. The paradoxical lack of effect of caffeine, as well as the inhibitory effect of tetrodotoxin, are discussed.

Original languageEnglish
Pages (from-to)648-653
Number of pages6
JournalJournal of Neuroscience Research
Volume38
Issue number6
StatePublished - 1994

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Keywords

  • caffeine
  • glutamate
  • metabotropic
  • N(ω)-nitro-L- arginine
  • N-methyl-D-aspartate (NMDA)

ASJC Scopus subject areas

  • Neuroscience(all)

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