Ozone-induced loss of neuronal M2 muscarinic receptor function is prevented by cyclophosphamide

L. M. Gambone, C. L. Elbon, Allison Fryer

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

We tested the hypothesis that inflammatory cells mediate the loss of neuronal M2 muscarinic receptors in the lung after ozone exposure. Pathogen- free guinea pigs treated with cyclophosphamide (30 mg · kg-1 · day-1 ip for 7 days) before exposure to ozone were compared with untreated ozone- exposed animals. This dose of cyclophosphamide significantly reduced leukocytes in peripheral blood and bronchoalveolar lavage fluid. Twenty-four hours after ozone, muscarinic receptor function was tested in anesthetized animals. In air-exposed guinea pigs, vagally induced bronchoconstriction was attenuated by the muscarinic agonist pilocarpine (0.1-100 μg/kg iv) and potentiated by the selective M2 antagonist gallamine (0.1-10 mg/kg iv), indicating that the neuronal M2 muscarinic receptors were functioning. These responses were significantly reduced after ozone, indicating loss of neuronal M2 muscarinic receptor function. However, in those animals treated with cyclophosphamide, M2 muscarinic receptor function was not altered by ozone. These data suggest that ozone-induced loss of neuronal muscarinic receptor function is mediated via inflammatory cells and that the link between ozone- induced hyperresponsiveness and inflammation may be the neuronal M2 muscarinic receptor.

Original languageEnglish (US)
Pages (from-to)1492-1499
Number of pages8
JournalJournal of Applied Physiology
Volume77
Issue number3
StatePublished - 1994
Externally publishedYes

Fingerprint

Muscarinic M2 Receptors
Ozone
Cyclophosphamide
Muscarinic Receptors
Guinea Pigs
Gallamine Triethiodide
Muscarinic Agonists
Pilocarpine
Bronchoconstriction
Bronchoalveolar Lavage Fluid
Leukocytes
Air
Inflammation
Lung

Keywords

  • gallamine
  • hyperresponsiveness
  • inflammation
  • inflammatory cells
  • parasympathetic nerves
  • pilocarpine

ASJC Scopus subject areas

  • Endocrinology
  • Physiology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Ozone-induced loss of neuronal M2 muscarinic receptor function is prevented by cyclophosphamide. / Gambone, L. M.; Elbon, C. L.; Fryer, Allison.

In: Journal of Applied Physiology, Vol. 77, No. 3, 1994, p. 1492-1499.

Research output: Contribution to journalArticle

@article{7408a465161549c48a0c72c29fa7db92,
title = "Ozone-induced loss of neuronal M2 muscarinic receptor function is prevented by cyclophosphamide",
abstract = "We tested the hypothesis that inflammatory cells mediate the loss of neuronal M2 muscarinic receptors in the lung after ozone exposure. Pathogen- free guinea pigs treated with cyclophosphamide (30 mg · kg-1 · day-1 ip for 7 days) before exposure to ozone were compared with untreated ozone- exposed animals. This dose of cyclophosphamide significantly reduced leukocytes in peripheral blood and bronchoalveolar lavage fluid. Twenty-four hours after ozone, muscarinic receptor function was tested in anesthetized animals. In air-exposed guinea pigs, vagally induced bronchoconstriction was attenuated by the muscarinic agonist pilocarpine (0.1-100 μg/kg iv) and potentiated by the selective M2 antagonist gallamine (0.1-10 mg/kg iv), indicating that the neuronal M2 muscarinic receptors were functioning. These responses were significantly reduced after ozone, indicating loss of neuronal M2 muscarinic receptor function. However, in those animals treated with cyclophosphamide, M2 muscarinic receptor function was not altered by ozone. These data suggest that ozone-induced loss of neuronal muscarinic receptor function is mediated via inflammatory cells and that the link between ozone- induced hyperresponsiveness and inflammation may be the neuronal M2 muscarinic receptor.",
keywords = "gallamine, hyperresponsiveness, inflammation, inflammatory cells, parasympathetic nerves, pilocarpine",
author = "Gambone, {L. M.} and Elbon, {C. L.} and Allison Fryer",
year = "1994",
language = "English (US)",
volume = "77",
pages = "1492--1499",
journal = "Journal of Applied Physiology",
issn = "8750-7587",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - Ozone-induced loss of neuronal M2 muscarinic receptor function is prevented by cyclophosphamide

AU - Gambone, L. M.

AU - Elbon, C. L.

AU - Fryer, Allison

PY - 1994

Y1 - 1994

N2 - We tested the hypothesis that inflammatory cells mediate the loss of neuronal M2 muscarinic receptors in the lung after ozone exposure. Pathogen- free guinea pigs treated with cyclophosphamide (30 mg · kg-1 · day-1 ip for 7 days) before exposure to ozone were compared with untreated ozone- exposed animals. This dose of cyclophosphamide significantly reduced leukocytes in peripheral blood and bronchoalveolar lavage fluid. Twenty-four hours after ozone, muscarinic receptor function was tested in anesthetized animals. In air-exposed guinea pigs, vagally induced bronchoconstriction was attenuated by the muscarinic agonist pilocarpine (0.1-100 μg/kg iv) and potentiated by the selective M2 antagonist gallamine (0.1-10 mg/kg iv), indicating that the neuronal M2 muscarinic receptors were functioning. These responses were significantly reduced after ozone, indicating loss of neuronal M2 muscarinic receptor function. However, in those animals treated with cyclophosphamide, M2 muscarinic receptor function was not altered by ozone. These data suggest that ozone-induced loss of neuronal muscarinic receptor function is mediated via inflammatory cells and that the link between ozone- induced hyperresponsiveness and inflammation may be the neuronal M2 muscarinic receptor.

AB - We tested the hypothesis that inflammatory cells mediate the loss of neuronal M2 muscarinic receptors in the lung after ozone exposure. Pathogen- free guinea pigs treated with cyclophosphamide (30 mg · kg-1 · day-1 ip for 7 days) before exposure to ozone were compared with untreated ozone- exposed animals. This dose of cyclophosphamide significantly reduced leukocytes in peripheral blood and bronchoalveolar lavage fluid. Twenty-four hours after ozone, muscarinic receptor function was tested in anesthetized animals. In air-exposed guinea pigs, vagally induced bronchoconstriction was attenuated by the muscarinic agonist pilocarpine (0.1-100 μg/kg iv) and potentiated by the selective M2 antagonist gallamine (0.1-10 mg/kg iv), indicating that the neuronal M2 muscarinic receptors were functioning. These responses were significantly reduced after ozone, indicating loss of neuronal M2 muscarinic receptor function. However, in those animals treated with cyclophosphamide, M2 muscarinic receptor function was not altered by ozone. These data suggest that ozone-induced loss of neuronal muscarinic receptor function is mediated via inflammatory cells and that the link between ozone- induced hyperresponsiveness and inflammation may be the neuronal M2 muscarinic receptor.

KW - gallamine

KW - hyperresponsiveness

KW - inflammation

KW - inflammatory cells

KW - parasympathetic nerves

KW - pilocarpine

UR - http://www.scopus.com/inward/record.url?scp=0028024096&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028024096&partnerID=8YFLogxK

M3 - Article

C2 - 7836157

AN - SCOPUS:0028024096

VL - 77

SP - 1492

EP - 1499

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

SN - 8750-7587

IS - 3

ER -