Mechanisms of M1 muscarinic receptor-mediated up-regulation of neuronal nitric oxide synthase in N1E-115 neuroblastoma cells

Adolfo E. Cuadra, Esam E. El-Fakahany

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4 Scopus citations

Abstract

The neuronal form of nitric oxide synthase (nNOS) was generally assumed to be constitutively expressed at a constant level. However, it is now becoming recognized that its expression can be modulated by a number of physiological and pathophysiological conditions. Previously, we reported that nNOS expression is up-regulated after prolonged muscarinic M1 receptor stimulation. In this work, we report that muscarinic receptor activation signals the up-regulation of nNOS via multiple pathways in N1E-115 mouse neuroblastoma cells. These include protein kinase C (PKC) activation, cytosolic calcium mobilization and NO production. Further characterization showed that the half-life of nNOS is slightly, but significantly, increased in agonist-pretreated cells compared with vehicle-treated control cells. Based on these data, it appears that the level of nNOS expression is modulated in a complex manner by a number of mechanisms that include, but might not be limited to, those described here.

Original languageEnglish (US)
Pages (from-to)198-204
Number of pages7
JournalMolecular Brain Research
Volume134
Issue number2
DOIs
StatePublished - Apr 4 2005

Bibliographical note

Funding Information:
This work was supported by NIH grant NS25743 (EEE) and its supplement (EAC).

Keywords

  • Cellular homeostasis
  • Enzyme expression
  • Signal transduction

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