SRS-A

Slow Reacting Substance of Anaphylaxis (SRS-A) is a group of bioactive lipids that play a critical role in the pathophysiology of asthma and other allergic reactions. SRS-A is primarily composed of leukotrienes, specifically leukotriene C4 (LTC4), leukotriene D4 (LTD4), and leukotriene E4 (LTE4). These substances are part of the eicosanoid family, which are derived from arachidonic acid, a polyunsaturated fatty acid found in the cell membrane.

Discovery

The existence of SRS-A was first postulated in the 1950s following observations that certain substances were released during anaphylactic reactions that caused slow, sustained smooth muscle contraction. It was not until the 1970s and 1980s, however, that the exact chemical nature of SRS-A was elucidated, revealing the crucial role of leukotrienes.

Biosynthesis

SRS-A is synthesized from arachidonic acid through the lipoxygenase pathway. This pathway involves the initial conversion of arachidonic acid to 5-hydroperoxyeicosatetraenoic acid (5-HPETE) by the enzyme 5-lipoxygenase. 5-HPETE is then further converted into leukotriene A4 (LTA4), which can be metabolized into LTC4, LTD4, and LTE4, the active components of SRS-A.

Function

SRS-A is known for its potent effects on the respiratory system. It causes constriction of bronchial smooth muscle, increased vascular permeability leading to edema, and mucus secretion, all of which contribute to the pathophysiology of asthma and allergic reactions. The effects of SRS-A are mediated through specific G protein-coupled receptors (GPCRs) on target cells, including leukotriene receptors such as BLT1, BLT2, CysLT1, and CysLT2.

Clinical Significance

Due to its significant role in allergic reactions and asthma, SRS-A has been a target for therapeutic intervention. Antileukotriene drugs, such as montelukast and zafirlukast, which block the action of leukotriene receptors, have been developed to treat asthma and allergic rhinitis. These medications help to alleviate symptoms by preventing the effects of SRS-A components.

Research Directions

Research continues to explore the role of SRS-A and leukotrienes in other inflammatory conditions and diseases. Understanding the complex pathways involved in the synthesis and action of these molecules may lead to the development of new therapeutic strategies for a variety of conditions.