Document Detail


The effect of the selective PAF antagonist CIS-19 on PAF- and antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity in guinea-pigs.
MedLine Citation:
PMID:  9050014     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated the effects of a novel platelet-activating factor (PAF) receptor antagonist, CIS-19 [cis-2-(3, 4-dimethoxyphenyl)-6-isopropoxy-7-methoxy-1-(N-methyl-formamido)-1, 2, 3, 4-tetrahydronaphthalene], on PAF-, histamine-, substance P- and antigen-induced bronchoconstriction and microvascular leakage, as well as PAF- and antigen-induced bronchial hyperreactivity to methacholine in urethane-anesthetized guinea-pigs. Administration of CIS-19 (0.5-5 mg/kg, i.v.) inhibited the increase in lung resistance induced by PAF (30 ng/kg, i.v.) in a dose-dependent manner, but failed to inhibit the increase induced by histamine (30 micrograms/kg, i.v.) or substance P (6.5 micrograms/kg, i.v.). CIS-19 (5 mg/kg, i.v.) did not inhibit the increase in lung resistance induced by ovalbumin (2 mg/kg, i.v.) in actively sensitized guinea-pigs. PAF (30 ng/kg, i.v.)-induced microvascular leakage, measured by the extravasation of Evans blue dye, was dose-dependently inhibited by CIS-19 (0.5-5 mg/kg, i.v.) in the trachea, main bronchi and intrapulmonary airways, but it did not affect histamine (30 micrograms/kg, i.v.)- or substance P (6.5 micrograms/kg, i.v.)-induced microvascular leakage at all airway levels. CIS-19 (2.5 and 5 mg/kg) did not affect ovalbumin (2 mg/kg, i.v.)-induced microvascular leakage in all airway levels in actively sensitized guinea-pigs, CIS-19 (2.5 and 5 mg/kg, i.v.) significantly inhibited PAF-induced enhancement of the bronchial response to methacholine, but had no effect on ovalbumin (0.05 mg/kg, i.v.)-induced bronchial hyperreactivity in actively sensitized guinea-pigs. It is concluded that CIS-19 is a potent PAF receptor antagonist which inhibits PAF- but not antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity. These results suggest that PAF plays little or no role in early airway responses following antigen challenge.
Authors:
C H Lin; F N Ko; H Ishii; T Ishikawa; I S Chen; C M Teng; H P Kuo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  355     ISSN:  0028-1298     ISO Abbreviation:  Naunyn Schmiedebergs Arch. Pharmacol.     Publication Date:  1997 Feb 
Date Detail:
Created Date:  1997-05-27     Completed Date:  1997-05-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  210-6     Citation Subset:  IM    
Affiliation:
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
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MeSH Terms
Descriptor/Qualifier:
Airway Resistance / drug effects
Animals
Antigens / immunology
Bronchoconstriction / drug effects*,  immunology
Bronchoconstrictor Agents / pharmacology
Capillary Permeability / drug effects*
Guinea Pigs
Histamine / pharmacology
Male
Methacholine Chloride / pharmacology
Platelet Activating Factor / toxicity
Platelet Membrane Glycoproteins / antagonists & inhibitors*
Rats
Receptors, Cell Surface*
Receptors, G-Protein-Coupled*
Respiratory Hypersensitivity / chemically induced,  immunology,  prevention & control*
Substance P / pharmacology
Tetrahydronaphthalenes / pharmacology*
Chemical
Reg. No./Substance:
0/Antigens; 0/Bronchoconstrictor Agents; 0/Platelet Activating Factor; 0/Platelet Membrane Glycoproteins; 0/Receptors, Cell Surface; 0/Receptors, G-Protein-Coupled; 0/Tetrahydronaphthalenes; 0/platelet activating factor receptor; 33507-63-0/Substance P; 51-45-6/Histamine; 62-51-1/Methacholine Chloride; 88114-56-1/CIS 19

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


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