Inhibition of excitatory neurotransmitter-nitric oxide signaling pathway by inhalational anesthetics

Z. Zuo, A. Tichotsky, R. A. Johns

Research output: Contribution to journalArticle

Abstract

Primary cultures of cerebral neurons of Sprague-Dawley rats increased cyclic GMP production in response to the stimulation of excitatory amino acids, including N-methyl-D-aspartate, quisqualate, kainate and (±)-1-aminocylopentane-trans-1,3-dicarboxylic acid. This increased cyclic GMP production was significantly inhibited by halothane or isoflurane at clinically relevant concentrations (0.5-2%). This inhibition was reversible by treatment with L-arginine, the substrate of nitric oxide synthase. However, the increase of cyclic GMP production stimulated by sodium nitroprusside, an activator of soluble guanylate cyclase, was not inhibited by halothane or isoflurane. Neither halothane nor isoflurane affected the basal cyclic GMP production.Activation of the excitatory amino acid neurotransmitter-stimulated nitric oxide-guanylate cyclase signaling pathway increases intracellular cyclic GMP content in neurons. Our results suggest that halothane or isoflurane inhibited this signaling pathway stimulated by selective agonists of each subtype of receptors for excitatory amino acid neurotransmitters. This inhibition may be involved in mechanisms of anesthesia and analgesia. The site(s) of the inhibition is (are) proximal to the activation of neuronal nitric oxide synthase. Copyright (C) 1999 IBRO.

Original languageEnglish (US)
Pages (from-to)1167-1172
Number of pages6
JournalNeuroscience
Volume93
Issue number3
DOIs
StatePublished - Aug 1 1999
Externally publishedYes

Keywords

  • Cyclic GMP
  • Excitatory amino acids
  • Inhalational anesthetics
  • Neuron
  • Neuronal nitric oxide synthase
  • Soluble guanylate cyclase

ASJC Scopus subject areas

  • Neuroscience(all)

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