Role of Cysteinyl Leukotrienes in Allergic Rhinitis.
Cysteinyl leukotrienes (CysLTs) are lipid mediators that have been implicated in the pathogenesis of allergic rhinitis. Pharmacological studies using CysLTs indicate that two classes of receptor exist: CysLT1 receptor (CysLT1R) and CysLT2 receptor (CysLT2R). The CysLT1R is a high-affinity leukotriene D4 receptor with lower affinity for leukotriene C4 that is sensitive to the CysLT1R antagonist currently used to treat asthma and allergic rhinitis. Our previous immunohistochemical and autoradiographic studies have demonstrated the presence of anti-CysLT1R antibodies labeled in eosinophils, mast cells, macrophages, neutrophils and vascular endothelial cells in human nasal mucosa. Furthermore, we have revealed that the novel radioactive CysLT1R antagonist [3H]-pranlukast bound specifically to CysLT1R in human inferior turbinates and its binding sites were localized to vascular endothelium and the interstitial cells. These data suggest that the major targets of CysLT1R antagonists in allergic rhinitis are the vascular bed and infiltrated leukocytes such as mast cells, eosinophils and macrophages. Clinical trials have demonstrated that CysLT1R antagonists are as effective as antihistamines for the treatment of allergic rhinitis; however, they are less effective than intranasal steroids. The use of CysLT1R antagonists in combination with antihistamines has generally resulted in greater efficacy than when these agents were used alone.
Hideaki
H
Shirasaki
Tetsuo
T
Himi
D003545:Cysteine / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators; D015289:Leukotrienes / Q000502:physiology*; D009297:Nasal Mucosa / Q000378:metabolism* / Q000473:pathology; D065631:Rhinitis, Allergic / Q000378:metabolism* / Q000473:pathology
D018836:Inflammation Mediators; D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D003545:Cysteine