Therapeutic target of leukotriene B4 receptors, BLT1 and BLT2: Insights from basic research.

Leukotriene B 4 (LTB 4) is a lipid mediator rapidly generated from arachidonic acid in response to various stimuli. This lipid mediator exerts its biological activities by binding to cognate receptors. Two LTB 4 receptors have been cloned; BLT1 and BLT2 as a high- and a low-affinity receptors, respectively. In numerous analyses, physiological and pathophysiological importance of LTB 4 and cognate receptors in various diseases has been clarified. For example, disruption of the BLT1 gene or treatment with blockers for this receptor reduced various diseases such as rheumatoid arthritis and bronchial asthma in mice, in contrast BLT2 deficiency facilitated several diseases in the small intestine and the skin. These data support the idea that BLT1 blockers and BLT2 agonists could be useful for the cure of these diseases. Thus, various drugs targeting each receptor are being developed by many pharmaceutical companies. In this review, we focus on our current knowledge of the biosynthesis and physiological roles of LTB 4 through cognate receptors. We further describe the effects of these receptor deficiencies on several pathophysiological conditions, including the potential of LTB 4 receptors as therapeutic targets for the cure of the diseases. Moreover, current information on the structure and post-translational modification of BLT1 and BLT2 is discussed. [Display omitted] • Leukotriene B 4 (LTB 4) is a lipid mediator generated from arachidonic acid. • BLT1 and BLT2 are a high- and a low-affinity LTB 4 receptor, respectively. • Importance of LTB 4 and cognate receptors in various diseases has been clarified. • We describe the potential of LTB 4 receptors as therapeutic targets. [ABSTRACT FROM AUTHOR]