Synergistic antiallergic activity of combined histamine H1- and cysteinyl leukotriene1-receptor blockade in human bronchus
| Autor: | LoriAnn M. Ruck, Robert W. Egan, John C. Anthes, Cuss Francis M, Stephen Eckel, John A. Hey, Charles A. Rizzo |
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| Rok vydání: | 2001 |
| Předmět: |
Adult
Male Leukotriene D4 Bronchi In Vitro Techniques Pharmacology General Biochemistry Genetics and Molecular Biology Bronchospasm chemistry.chemical_compound medicine Humans Mast Cells General Pharmacology Toxicology and Pharmaceutics Zafirlukast Cells Cultured Receptors Leukotriene Leukotriene Bronchus Bronchial Spasm Dose-Response Relationship Drug business.industry Immunization Passive Membrane Proteins Drug Synergism Muscle Smooth General Medicine Immunoglobulin E Middle Aged respiratory system Histamine H1 Antagonists Mast cell respiratory tract diseases medicine.anatomical_structure chemistry Immunology Quinolines Leukotriene Antagonists Female Propionates medicine.symptom business Histamine Muscle Contraction medicine.drug |
| Zdroj: | Life Sciences. 68:2825-2834 |
| ISSN: | 0024-3205 |
| Popis: | Mast cell histamine (HA) and cysteinyl leukotrienes (CysLT) account for most of the early phase bronchospasm in asthma. However, activation of the smooth muscle CysLT1-receptor plays a major role in asthmatic bronchospasms. CysLT-receptor antagonists or CysLT-synthesis inhibitors are efficacious in asthma but do not completely abolish asthmatic bronchospasms. A recent clinical study showed that combined antagonists loratadine (H1) and zafirlukast (CysLT1) were more effective against allergic bronchospasms than either drug alone. We examined the combined efficacy of H1- and CysLT1-receptor antagonists in allergic human bronchus. The H1- and CysLT1-receptor antagonists chlorpheniramine (CTM; 1 microM) and MK-571 (0.03 microM), were tested alone and in combination, against anti-human IgE antibody (Ab)-induced contractions of passively sensitized isolated human bronchus. Ab-induced allergic contractions were reduced 15% and 36% by CTM (1 microM) and MK-571 (0.03 microM), respectively. Combined CTM (1 microM) and MK-571 (0.03 microM) significantly inhibited the Ab response by 87%. Mechanistic investigations in isolated human bronchus and cultured human cord blood mast cells suggest that H1- and CysLT-receptor interactions likely occur at the airway smooth muscle level. CTM and MK-571 synergistically inhibited human allergic bronchospasm in the present in vitro model. The mechanism underlying this synergistic activity requires further investigation. |
| Databáze: | OpenAIRE |
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