Anaphylaxis SRS

Slow-reacting substance of anaphylaxis (SRS-A) is a mixture of leukotrienes C4, D4, and E4. This mixture of leukotrienes is a potent constrictor of the bronchial ait-way musculature. These leukotrienes together with leukotriene B4 also cause vascular permeabifity and attraction and activation of leukocytes and ate important regulators in many diseases involving inflammatory or... 

In the 1930s an unknown material was hypothesized that was proposed to cause a slow and sustained contraction of smooth muscle. It was named the slow reacting substance (SRS). By 1940 a similar substance was reported to be found in guinea pig lungs and was called the slow reacting substance of anaphylaxis (SRS-A). Over the next 40 years, while no one could isolate, characterize, or synthesize this mate-... 

LTC4 and LTD4 are potent bronchoconstrictors and are recognized as the primary components of the slow-reacting substance of anaphylaxis (SRS-A) that is secreted in asthma and anaphylaxis. There are four current approaches to antileukotriene drug development 5-LOX enzyme inhibitors, leukotriene-receptor antagonists, inhibitors of FLAP, and phospholipase A2 inhibitors. 

Eosinophils are attracted by proteins released by T cells, mast cells and basophils [eosinophil chemotactic factor of anaphylaxis (ECF-A)]. They bind schistosomulae coated with IgG or IgE, degranulate and release major basic protein, which is toxic. Eosinophils also release histaminase and aryl sulfatase, which inactivates histamine and Slow reacting substance of anaphylaxis (SRS-A). This results in antiinflammatory effects and inhibits migration of granulocytes to the site of injury. 

Corey, E.J., Albright, ).0., Burton, A.E. and Hashimoto, S. (1980) Chemical and enzymic syntheses of 5-HPETE, a key biological precursor of slow-reacting substance of anaphylaxis (SRS), and 5-HETE. Journal of the American Chemical Society, 102,1435-1436. 

Most cases of contact urticaria are of non-immunolo-gical origin, presumably due to the direct release of histamine, slow-reacting substance of anaphylaxis (SRS-A), bradykinin, or other vasoactive substances. Topical drugs and ingredients of cosmetics that have caused non-immunological contact urticaria are listed in Table 2. 

It is curious that it has also been reported that aspirin could relieve asthmatic bron-choconstriction. Earlier, an endogenous substance called Slow Reacting Substance in Anaphylaxis (SRS-A), which is able to contract isolated human bronchial tissue, was reported to be produced during human anaphylactic shock. It was suggested that aspirin antagonism of SRS-A-caused bronchoconstriction might be useful for asthma relief. This suggestion, however, has not been clinically implemented. 

Beta-agonists, indirectly via c-AMP, act on mast cell p2-receptors inhibiting the release of bronchoconstrictor mediators such as histamine. Slow-reacting substance of anaphylaxis (SRS-A), now known to be leukotriene D3 and D4 (Fig. 5-5), and eosinophil chemo-tactic factor of anaphylaxis (ECF-A) may also have their release inhibited by c-AMP. Leukotriene D, which is a mediator of hypersensitivity reactions, may still have an important role in causing asthmatic symptoms. In fact, it is 100 times more effective than histamine in producing vascular permeability. 

---