Document Detail


Effect of the selective thromboxane A2 receptor antagonist, S-1452, on antigen-induced sustained bronchial hyperresponsiveness.
MedLine Citation:
PMID:  7988644     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Long-lasting bronchial hyperresponsiveness to i.v. acetylcholine was observed in actively sensitized guinea-pigs after aerosol ovalbumin exposure. The response became significant at 7 h post-challenge and persisted for at least 120 h compared to the response of unsensitized animals. Pretreatment of animals with the specific thromboxane A2 receptor antagonist, S-1452 (calcium (1R,2S,3S,4S)-(5Z)-7-(((phenylsulfonyl)amino)bicyclo[2.2.1] hept-2-yl)hept-5-enoate dihydrate), almost completely inhibited the onset of bronchial hyperresponsiveness, as assessed at 24 and 120 h post-challenge. However, it was ineffective when administered at 1 h post-challenge or 2 h before assessment of bronchial responsiveness. Lung vascular injury occurred transiently immediately after antigen challenge, the kinetics of injury being associated with those for the production of thromboxane B2 in bronchoalveolar lavage fluid. The vascular injury was dramatically suppressed by pretreatment with S-1452. These findings suggest that acutely generated thromboxane A2 plays an important role in the pathogenesis of antigen-induced long-lasting bronchial hyperresponsiveness, probably by producing vascular damage in the lungs.
Authors:
A Arimura; F Asanuma; Y Matsumoto; A Kurosawa; H Jyoyama; H Nagai
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of pharmacology     Volume:  260     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1994 Aug 
Date Detail:
Created Date:  1995-01-09     Completed Date:  1995-01-09     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  201-9     Citation Subset:  IM    
Affiliation:
Discovery Research Laboratories II, Shionogi & Co., Ltd. Osaka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / administration & dosage,  pharmacology
Administration, Inhalation
Aerosols
Animals
Asthma / drug therapy
Bicyclo Compounds / administration & dosage,  pharmacology,  therapeutic use*
Bronchial Hyperreactivity / drug therapy*
Bronchoalveolar Lavage Fluid / chemistry,  cytology
Disease Models, Animal
Endothelium, Vascular / drug effects,  pathology,  ultrastructure
Fatty Acids, Monounsaturated / administration & dosage,  pharmacology,  therapeutic use*
Guinea Pigs
Immunization
Injections, Intravenous
Lung / blood supply,  pathology
Male
Ovalbumin / administration & dosage,  toxicity
Prostaglandins / metabolism
Pulmonary Artery / drug effects,  pathology,  ultrastructure
Receptors, Prostaglandin / antagonists & inhibitors*
Thromboxane A2 / metabolism
Chemical
Reg. No./Substance:
0/Aerosols; 0/Bicyclo Compounds; 0/Fatty Acids, Monounsaturated; 0/Prostaglandins; 0/Receptors, Prostaglandin; 112966-96-8/S 145; 51-84-3/Acetylcholine; 57576-52-0/Thromboxane A2; 9006-59-1/Ovalbumin

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


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