Inhibition of neuronal M 2 muscarinic receptor function in the lungs by extracellular nitric oxide

L. Golkar, K. A. Yarkony, Allison Fryer

Research output: Contribution to journalArticle

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Abstract

1. These experiments were carried out to test whether neuronal M 2 muscarinic receptor function in the lungs is affected by nitric oxide (NO) and whether the source of the NO is epithelial or neuronal. 2. In pathogen free, anaesthetized guinea-pigs, the muscarinic agonist pilocarpine inhibited vagally induced bronchoconstriction demonstrating functional neuronal M 2 muscarinic receptors. In the presence of the NO donor, 3-morpholino-sydnonimine (SIN-1), pilocarpine no longer inhibited vagally induced bronchoconstriction. In contrast, inhibiting endogenous NO with N(G)-monomethyl-L-arginine methyl ester (L-NMMA) did not affect the ability of pilocarpine to decrease vagally induced bronchoconstriction. 3. In isolated tracheas, pilocarpine inhibited contractions induced by electrical field stimulation demonstrating that neuronal M 2 muscarinic receptors function in vitro. As in the anaesthetized guinea-pigs, SIN-1 shifted the pilocarpine dose response curve to the right, demonstrating decreased neuronal M 2 receptor function. However, in vitro, L-NMMA shifted the pilocarpine dose response curve to the left, demonstrating that endogenous NO was inhibiting the ability of the M 2 receptors to decrease acetylcholine (ACh) release. 4. Both haemoglobin (Hb), which scavenges NO, and epithelial removal also shifted the pilocarpine dose response curve to the left, demonstrating that the NO inhibiting neuronal M 2 receptor function was extracellular and probably of epithelial origin. 5. In conclusion, extracellular NO appears to inhibit the ability of the M: receptors to decrease ACh release from the parasympathetic nerves in the lungs in viva and in vitro in pathogen free guinea-pigs. However, while the neuronal M 2 receptors will respond to NO (from SIN-1) in vivo, there does not appear to be an endogenous source of NO since L-NMMA had no effect in vivo.

Original languageEnglish (US)
Pages (from-to)312-318
Number of pages7
JournalBritish Journal of Pharmacology
Volume131
Issue number2
Publication statusPublished - 2000
Externally publishedYes

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Keywords

  • Airway epithelium
  • L-NMMA, pilocarpine
  • Neuronal M receptors
  • Nitric oxide
  • SIN-1

ASJC Scopus subject areas

  • Pharmacology

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