Heterogeneous effect of leucotriene CysLT1 receptor antagonists on antigen-induced motor and inflammatory responses in guinea-pig airways.
1. The effect of montelukast or MEN91507, selective leucotriene CysLT1 receptor antagonists, on antigen-induced airway inflammation and bronchoconstriction were compared in anaesthetized guinea-pigs. 2. In sensitized animals, ovalbumin (0.3 mg kg(-1), i.v.)-induced microvascular leakage in trachea, intrapulmonary airways, total lung (parenchyma and intrapulmonary airways) and urinary bladder was reduced by MEN91507 (0.01-1 micromol kg(-1), i.v.), whereas montelukast (0.01-1 micromol kg(-1), i.v.) antagonized the effect of the antigen only in the lung and urinary bladder. 3. Ovalbumin (1 mg kg(-1), i.v.)-induced bronchoconstriction was dose dependently antagonized by MEN91507 (10-30 micromol kg(-1), i.v.), whereas the effect of montelukast (0.1-30 micromol kg(-1), i.v.) was marginal (15-30% inhibition). Neither MEN91507 nor montelukast (30 micromol kg(-1), i.v.) affected the bronchoconstrictor response induced by acetylcholine (0.3 micromol kg(-1), i.v.) in sensitized animals. 4. It is concluded that montelukast and MEN91507 display a differential activity against the effect of endogenous leucotrienes, despite the fact that both compounds show a similar antagonist profile against exogenous leucotrienes acting through CysLT1 receptors.
Alfieri
A B
AB
Department of Pharmacology, School of Pharmacy, Central University of Venezuela, Caracas, Venezuela.
Tramontana
M
M
Cialdai
C
C
Lecci
A
A
Giuliani
S
S
Crea
A
A
Manzini
S
S
Maggi
C A
CA
D000085:Acetates / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001578:Benzopyrans / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects*; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D005070:Evans Blue; D006168:Guinea Pigs; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D007275:Injections, Intravenous; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D010047:Ovalbumin / Q000008:administration & dosage / Q000494:pharmacology; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology; D018077:Receptors, Leukotriene; D012137:Respiratory System / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology*; D013440:Sulfides; D013777:Tetrazoles / Q000494:pharmacology
D000085:Acetates; D000941:Antigens; D001578:Benzopyrans; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; C471346:MEN91507; D008565:Membrane Proteins; D011804:Quinolines; D018077:Receptors, Leukotriene; D013440:Sulfides; D013777:Tetrazoles; D005070:Evans Blue; D010047:Ovalbumin; C083169:leukotriene D4 receptor; C093875:montelukast