Binding to Cysteinyl-Leukotriene Receptors

It is widely accepted that leukotrienes (LTs) exert their actions through high-affinity specific receptors, although only the LTB 4 receptor has been cloned so far (1). Given the differences between the two classes of LTs (LTB 4 versus LTC 4 , LTD 4 , and LTE 4 , i.e., cysteine-containing leukotrienes or cysteinyl-LTs) in terms of both structure and profile of biological activity, it is not unexpected that the receptors for LTB 4 are totally different from those for cysteinyl-LTs and no cross-reactivity has been shown among the two classes. The first hint of the existence of leukotriene receptors had been given even before their structure had been elucidated. FPL-55712 had been proposed as an antagonist of slow-reacting substance of anaphylaxis (SRS-A) when it was not yet known that the latter was composed mainly of LTs (2). Subsequently, the recognition of strict structural requirements for LT action (3, 4), their high potency (in the nanomolar range), and the development of a number of specific antagonists (5) made it clear that these lipid mediators elicit their biological actions through specific receptors. The existence of different classes of Cys-LT receptors in human tissues is the subject of this article. Cysteinyl-LTs have been recognized to play a key role in asthma (6), and, as a consequence, the large majority of studies aimed at the characterization of their receptors have been performed in the respiratory system. Asthma is a multifactorial disease, characterized by the presence of reversible airway obstruction, inflammation, and hyperresponsiveness (7). The most significant discovery in the more recent research on asthma pathophysiology has been the revelation that airway inflammation is the key component of this condition. Of the different mediators that are known to be involved in asthma, leukotrienes are considered to be among the most important because they participate both in bronchoconstriction and in the inflammatory component of this disease.