Document Detail

The effect of compound 48/80 on contractions induced by toluene diisocyanate in isolated guinea-pig bronchus.
MedLine Citation:
PMID:  7687959     Owner:  NLM     Status:  MEDLINE    
We have investigated the ability of compound 48/80 and of histamine H1 and H2 receptor antagonists to inhibit toluene diisocyanate-induced contractions in isolated guinea-pig bronchi. Compound 48/80 (100 micrograms/ml) significantly inhibited toluene diisocyanate-induced contractions. By contrast, the two histamine H1 and H2 receptor antagonists, chlorpheniramine (10 microM) and cimetidine, (10 microM) did not affect toluene diisocyanate-induced contractions, but significantly inhibited contractions induced by exogenously applied histamine (100 microM) and by 48/80. We investigated which mechanisms 48/80 used to inhibit toluene diisocyanate-induced contractions, paying particular attention to the possible involvement of capsaicin-sensitive primary afferents. In vitro capsaicin desensitization (10 microM for 30 min followed by washing) significantly reduced compound 48/80-induced contractions. A capsaicin-resistant component of contraction was also evident. Ruthenium red (3 microM), an inorganic dye which acts as a selective functional antagonist of capsaicin, did not affect 48/80-induced contraction. MEN 10,207 (Tyr5,D-Trp6,8,9,Arg10)-neurokinin A (4-10) (3 microM) a selective antagonist of NK2-tachykinin receptors significantly reduced 48/80-induced contractions. These results show that compound 48/80 inhibits toluene diisocyanate-induced contractions in isolated guinea-pig bronchi. It is likely that two mechanisms are involved in the inhibition: (1) the release of mediators other than histamine by mast cells, (2) an effect of 48/80 on sensory nerves.
C E Mapp; A Boniotti; A Papi; P Chitano; E Coser; A Di Stefano; M Saetta; A Ciaccia; L M Fabbri
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  248     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1993 Jun 
Date Detail:
Created Date:  1993-09-01     Completed Date:  1993-09-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  67-73     Citation Subset:  IM    
Institute of Occupational Medicine, University of Padua, Italy.
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MeSH Terms
Bronchoconstriction / drug effects*
Capsaicin / pharmacology
Cell Degranulation / drug effects
Glycopeptides / pharmacology
Guinea Pigs
Histamine H1 Antagonists / pharmacology
Histamine H2 Antagonists / pharmacology
Mast Cells / drug effects,  ultrastructure
Muscle Contraction / drug effects
Muscle, Smooth / drug effects*
Neprilysin / antagonists & inhibitors
Neurokinin A / analogs & derivatives,  pharmacology
Peptide Fragments / pharmacology
Ruthenium Red / pharmacology
Toluene 2,4-Diisocyanate / antagonists & inhibitors*,  pharmacology
p-Methoxy-N-methylphenethylamine / pharmacology*
Reg. No./Substance:
0/Glycopeptides; 0/Histamine H1 Antagonists; 0/Histamine H2 Antagonists; 0/Peptide Fragments; 11103-72-3/Ruthenium Red; 126050-12-2/neurokinin A (4-10), Tyr(5)-Trp(6,8,9)-Arg(10)-; 36357-77-4/phosphoramidon; 404-86-4/Capsaicin; 4091-50-3/p-Methoxy-N-methylphenethylamine; 584-84-9/Toluene 2,4-Diisocyanate; 86933-74-6/Neurokinin A; EC

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