Inhibition of Nitric Oxide Synthase Blocks N‐Methyl‐D‐Aspartate‐, Quisqualate‐, Kainate‐, Harmaline‐, and Pentylenetetrazole‐Dependent Increases in Cerebellar Cyclic GMP In Vivo

Paul L. Wood, Mark R. Emmett, Tadimeti S. Rao, Julie Cler, Steve Mick, Smriti Iyengar

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

Abstract

Abstract: The synthesis of nitric oxide by brain slices has been demonstrated in several laboratories. In addition, in vitro studies have demonstrated stimulation of nitric oxide synthesis by excitatory amino acid receptor agonists. These data have led to the hypothesis that this readily diffusible “intercellular messenger molecule”acts to generate a cascade effect by activating guanylate cyclase in several cell types and thereby augment levels of the second messenger cyclic GMP (cGMP). Therefore, we evaluated this hypothesis in vivo, by testing the actions of the nitric oxide synthase inhibitor N‐monomethyl‐L‐arginine (NMMA) on elevations in level of mouse cerebellar cGMP generated by excitatory amino acid receptor agonists. The stimulatory effects of D‐serine, quisqualate, and kainate were all found to be antagonized by this enzyme inhibitor. In addition, NMMA antagonized the increases in cerebellar cGMP level elicited by harmaline and pentylenetetrazole, pharmacological agents that augment endogenous excitatory amino acid transmission. Our data are, therefore, the first in vivo demonstration that nitric oxide is an important “messenger molecule”in the cerebellum, mediating the actions of kainate, quisqualate, and N‐methyl‐D‐aspartate receptor agonists on guanylate cyclase. These data are consistent with previous in vitro findings with kainate and N‐methyl‐D‐aspartate.

Original languageEnglish (US)
Pages (from-to)346-348
Number of pages3
JournalJournal of neurochemistry
Volume55
Issue number1
DOIs
StatePublished - Jul 1990
Externally publishedYes

Keywords

  • Cerebellum
  • Cyclic GMP
  • D‐Serine
  • Harmaline
  • Kainate
  • Nitric oxide
  • N‐Methyl‐D‐aspartate
  • N‐Monomethyl‐L‐arginine
  • Pentylenetetrazole
  • Quisqualate

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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