Leucotriene d4

All cysteinyl leukotrienes bind with different affinity to 2 G-protein bound receptors: CYSLTR1 and CYSLTR2 (CYSLTR = acronym for "cysteinyl leukotriene receptor"). These receptors play an essential role in the endocrine and cardiovascular system. Mast cells and monocytes, among others, express this type of receptor. The stimulation of mast cells by LTD4 increases the c-kit induced proliferation of mast cells.

LTD4 expressions activate numerous so-called "immediate early genes - IEG", transcription factors, cytokines, and membrane receptors. In this broad reactivity LTD4 acts analogous to LTB4.

The group of cysteinyl-leukotrienes induces vasoconstriction and bronchoconstriction in the lung. At the bronchial muscles, this leukotriene group has a 1000 times stronger constrictive effect than histamine. They are important mediators in human bronchial asthma and allergic rhinitis.

Furthermore, LTD4 and LTC4 have a strong vasoconstrictive effect on the coronary arteries. Likewise, the smooth muscles of the gastrointestinal tract are contractively excited by the cysteinyl leukotrienes.

In animal experiments, the cysteinyl leukotrienes lead to a disturbance of the microcirculation of the mucosa of the stomach. The substances thus potentiate the effect of other noxious agents.

LTD4 and PGE2 add their vascular-inflammatory responses such as increased permeability, edema and local pain formation in animal experiments.

Blocking the CYSLTR1 and CYSLTR2 receptors by leukotriene receptor antagonists (e.g. zafirlukast, montelukast) have a beneficial antiasthmatic effect.

Montelukast binds to the CYSLTR1 receptors and thus prevents the effects of cysteinyl leukotrienes with regard to inflammatory action and increased mucus secretion.

Like LTC4 and LTE4, inflammatory leukotriene D4 (LTD4) belongs to the cysteinyl leukotrienes and has a direct, leukocyte-independent, increasing effect on the permeability of postcapillary venules of various vascular regions. LTD-4 is released by basophilic granulocytes and mast cells, among others.

All cysteinyl leukotrienes bind with different affinity to 2 G-protein bound receptors: CYSLTR1 and CYSLTR2 (CYSLTR = acronym for "cysteinyl leukotriene receptor"). These receptors play an essential role in the endocrine and cardiovascular system. Mast cells and monocytes, among others, express this type of receptor. The stimulation of mast cells by LTD4 increases the c-kit induced proliferation of mast cells.

1. Al-Azzam N et al (2015) Modulation of mast cell proliferative and inflammatory responses by leukotriene d4 and stem cell factor signaling interactions. J Cell Physiol 230:595-602.
2. Chen LY et al (2011) Cooperative and redundant signaling of leukotriene B4 and leukotriene D4 in human monocytes. Allergy 66:1304-1311.
3. Dahlén B et al. (2012) Salbutamol but not ipratropium abolishes leukotriene D4-induced gas exchange abnormalities in asthma. Eur J Clin Pharmacol 68:1375-1383.
4. Guan WJ et al (2015) Leukotriene D4 inhalation challenge for predicting short-term efficacy of montelukast: a pilot study. Clin Respir J 9:111-120.
5. Kondeti V et al (2016) Leukotriene D4 and prostaglandin E2 signals synergize and potentiate vascular inflammation in a mast cell-dependent manner through cysteinyl leukotriene receptor 1 and E-prostanoid receptor 3 J Allergy Clin Immunol 137:289-298.