The effect of compound 48/80 on contractions induced by toluene diisocyanate in isolated guinea-pig bronchus.
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.
Mapp
C E
CE
Institute of Occupational Medicine, University of Padua, Italy.
Boniotti
A
A
Papi
A
A
Chitano
P
P
Coser
E
E
Di Stefano
A
A
Saetta
M
M
Ciaccia
A
A
Fabbri
L M
LM
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects; D006020:Glycopeptides / Q000494:pharmacology; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000648:ultrastructure; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D015260:Neprilysin / Q000037:antagonists & inhibitors; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D012430:Ruthenium Red / Q000494:pharmacology; D014051:Toluene 2,4-Diisocyanate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
D006020:Glycopeptides; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D010446:Peptide Fragments; D012430:Ruthenium Red; C063615:neurokinin A (4-10), Tyr(5)-Trp(6,8,9)-Arg(10)-; D014051:Toluene 2,4-Diisocyanate; D003189:p-Methoxy-N-methylphenethylamine; D015288:Neurokinin A; D015260:Neprilysin; D002211:Capsaicin; C008890:phosphoramidon