Document Detail


Ozone-induced loss of neuronal M2 muscarinic receptor function is prevented by cyclophosphamide.
MedLine Citation:
PMID:  7836157     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 i.p. 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 micrograms/kg i.v.) and potentiated by the selective M2 antagonist gallamine (0.1-10 mg/kg i.v.), 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.
Authors:
L M Gambone; C L Elbon; A D Fryer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  77     ISSN:  8750-7587     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  1994 Sep 
Date Detail:
Created Date:  1995-02-28     Completed Date:  1995-02-28     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1492-9     Citation Subset:  IM    
Affiliation:
Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205.
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MeSH Terms
Descriptor/Qualifier:
Anesthesia
Animals
Bronchial Hyperreactivity / pathology
Bronchoalveolar Lavage Fluid / cytology
Cyclophosphamide / pharmacology*
Gallamine Triethiodide / pharmacology
Guinea Pigs
Leukocyte Count / drug effects
Lung / metabolism,  pathology
Male
Muscarinic Antagonists / pharmacology*
Neurons / drug effects*
Ozone / antagonists & inhibitors*,  toxicity
Pilocarpine / pharmacology
Pneumonia / chemically induced,  metabolism,  pathology
Receptors, Muscarinic / drug effects*
Respiratory Mechanics / drug effects
Grant Support
ID/Acronym/Agency:
ES-05255/ES/NIEHS NIH HHS; HL-44727/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Muscarinic Antagonists; 0/Receptors, Muscarinic; 10028-15-6/Ozone; 50-18-0/Cyclophosphamide; 65-29-2/Gallamine Triethiodide; 92-13-7/Pilocarpine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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