Leukotrienes play a key role in asthma in three ways: causing inflammation, bronchoconstriction and mucus production. The cysteinyl leukotrienes (LTC 4, LTD 4 and LTE 4 ) have been shown to be the most potent bronchconstrictors in humans and are believed to play a crucial role in asthmatic airway obstruction.
Cysteinyl leukotrienes also promote the generation of chemokines and cytokines from airway smooth muscle, increase the expression of histamine receptors, amplify the effects of tachykinins in the airway, and have a role in the structural changes in the airway seen in asthma. There are two classes of drugs that are used to decrease the 6.
3 Leukotriene Antagonists. indications. Because leukotrienes are products of arachadonic acid metabolism and released by mast cells as potent mediators capable of inducing a plethora of physiological actions, inhibition of leukotrienes can directly affect symptoms associated with allergic disease.
LTC 4, LTD 4, LTE 4 and LTF 4 are often called cysteinyl leukotrienes due to the presence of the amino acid cysteine in their structure. The cysteinyl leukotrienes make up the slowreacting substance of anaphylaxis (SRSA). The most widely used class is the cysteinyl type 1 receptor antagonists, which block binding of the cysteinyl leukotrienes to the cell. The second class is an inhibitor of the 5lipoxygenase enzyme that prevents synthesis of both Experimental drugs are also available that inhibit leukotriene synthesis by inhibition of FLAP.
The rearrangement of 5HPETE to form the unstable LTA 4 is the ratelimiting step in the synthesis of the leukotrienes. This step is catalysed by LTA synthase. Leukotrienes are involved in leukocyte chemotaxis, tissue edema, mucus secretion, and smoothmuscle proliferation and bronchoconstriction. These properties have provided a rationale for the clinical development of leukotriene synthesis inhibitors and selective leukotriene receptor antagonists for treating of asthma.
In accordance, another disorder of cysteinyl LT metabolism, LTC 4 synthesis deficiency, has been found to be associated with a fatal developmental syndrome, including severe muscular hypotonia, psychomotor retardation, failure to thrive, and microcephaly (24, 25). Regulation of cysteinyl leukotriene receptor function As is the case for the cysLT synthesis, cellular responsiveness to cysLTs can be Jun 01, 2006 Cysteinyl leukotrienes (CysLTs) are a family of inflammatory Cysteinyl leukotrienes synthesis essay mediators synthesized from arachidonic acid by a variety of cells, including mast cells, eosinophils, basophils, and macrophages.
This article reviews the data for the role of CysLTs as multifunctional mediators in allergic rhinitis (AR).