Double-stranded RNA causes airway hyperreactivity and neuronal M2 muscarinic receptor dysfunction

William M.L. Bowerfind, Allison D. Fryer, David B. Jacoby

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Viral infection causes dysfunction of inhibitory M2 muscarinic receptors (M2Rs) on parasympathetic nerves, leading to airway hyperreactivity. The mechanisms of M2R dysfunction are incompletely understood. Double-stranded RNA (dsRNA), a product of viral replication, promotes the expression of interferons. Interferon-γ decreases M2R gene expression in cultured airway parasympathetic neurons. In this study, guinea pigs were treated with dsRNA (1 mg/kg ip) on 2 consecutive days. Twenty-four hours later, anesthetized guinea pigs had dysfunctional M2Rs and were hyperresponsive to electrical stimulation of the vagus nerves, in the absence of inflammation. DsRNA did not affect either cholinesterase or the function of postjunctional M3 muscarinic receptors on smooth muscle. M2Rs on the nerves supplying the heart were also dysfunctional, but M2Rs on the heart muscle itself functioned normally. Thus dsRNA causes increased bronchoconstriction and bradycardia via increased release of ACh from the vagus nerves because of loss of M2R function on parasympathetic nerves in the lungs and heart. Production of dsRNA may be a mechanism by which viruses cause dysfunction of neuronal M2Rs and airway hyperreactivity.

Original languageEnglish (US)
Pages (from-to)1417-1422
Number of pages6
JournalJournal of Applied Physiology
Volume92
Issue number4
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

Keywords

  • Asthma
  • Interferon
  • Parasympathetic nerves
  • Protein kinase R
  • Viral infection

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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