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

L. M. Gambone, C. L. Elbon, A. D. Fryer

Research output: Contribution to journalArticle

35 Scopus citations

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
DOIs
StatePublished - Jan 1 1994

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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