Effects of neurokinin receptor antagonists in virus-infected airways

David B. Jacoby, Bethany L. Yost, Thomas Elwood, Allison D. Fryer

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


We investigated the effects of a neurokinin-1 (NK1) receptor antagonist (SR-140333) and a NK2 receptor antagonist (SR-48968) on airway responsiveness and on the function of neuronal M2 muscarinic receptors, which normally inhibit vagal acetylcholine release, in guinea pigs infected with parainfluenza virus. Antagonists were given 1 h before infection and daily thereafter. Four days later, bronchoconstriction induced by either intravenous histamine (which is partly vagally mediated) or electrical stimulation of the vagus nerves was increased by viral infection compared with control. In addition, the ability of the muscarinic agonist pilocarpine to inhibit vagally induced bronchoconstriction was lost in virus-infected animals, demonstrating loss of neuronal M2 receptor function. Macrophage influx into the lungs was inhibited by pretreatment with both antagonists. However, only the NK1 receptor antagonist prevented M2 receptor dysfunction and inhibited hyperresponsiveness (measured as an increase in either vagally induced or histamine-induced bronchoconstriction). Thus virus-induced M2 receptor dysfunction and hyperresponsiveness are prevented by a NK1 receptor antagonist, but not by a NK2 receptor antagonist, whereas both antagonists had similar anti-inflammatory effects.

Original languageEnglish (US)
Pages (from-to)L59-L65
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number1 23-1
StatePublished - Jul 2000
Externally publishedYes


  • Asthma
  • Histamine
  • Parasympathetic nerves
  • Vagus nerves
  • Virus

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


Dive into the research topics of 'Effects of neurokinin receptor antagonists in virus-infected airways'. Together they form a unique fingerprint.

Cite this