Effects of neurokinin receptor antagonists in virus-infected airways

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

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume279
Issue number1 23-1
StatePublished - Jul 2000
Externally publishedYes

Fingerprint

Neurokinin-1 Receptor Antagonists
Bronchoconstriction
Viruses
Histamine
Muscarinic M2 Receptors
Paramyxoviridae Infections
Muscarinic Agonists
Pilocarpine
Vagus Nerve
Virus Diseases
Electric Stimulation
Acetylcholine
Guinea Pigs
Anti-Inflammatory Agents
Macrophages
Lung
Infection

Keywords

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

ASJC Scopus subject areas

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

Cite this

Effects of neurokinin receptor antagonists in virus-infected airways. / Jacoby, David; Yost, Bethany L.; Elwood, Thomas; Fryer, Allison.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 279, No. 1 23-1, 07.2000.

Research output: Contribution to journalArticle

@article{5ebecc42f270486b98774c61327b1b60,
title = "Effects of neurokinin receptor antagonists in virus-infected airways",
abstract = "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.",
keywords = "Asthma, Histamine, Parasympathetic nerves, Vagus nerves, Virus",
author = "David Jacoby and Yost, {Bethany L.} and Thomas Elwood and Allison Fryer",
year = "2000",
month = "7",
language = "English (US)",
volume = "279",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "1 23-1",

}

TY - JOUR

T1 - Effects of neurokinin receptor antagonists in virus-infected airways

AU - Jacoby, David

AU - Yost, Bethany L.

AU - Elwood, Thomas

AU - Fryer, Allison

PY - 2000/7

Y1 - 2000/7

N2 - 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.

AB - 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.

KW - Asthma

KW - Histamine

KW - Parasympathetic nerves

KW - Vagus nerves

KW - Virus

UR - http://www.scopus.com/inward/record.url?scp=0033863877&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033863877&partnerID=8YFLogxK

M3 - Article

C2 - 10893203

AN - SCOPUS:0033863877

VL - 279

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 1 23-1

ER -