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Chemical Compound Review

leukotriene D4     (5S,6R,7E,9E,11Z,14Z)-6- [(2S)-2-amino-2...

Synonyms: AC1NQXPJ, CHEMBL288943, BSPBio_001368, CHEBI:28666, LMFA03020006, ...
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Disease relevance of leukotriene D4

  • We found leukotriene C4 and leukotriene D4 in the lung lavage fluids of all five newborns who had the clinical diagnosis of persistent pulmonary hypertension and who required ventilatory assistance [1].
  • Leukotriene D4 (LTD4), a component of slow reacting substance of anaphylaxis (SRS-A)1, produces marked hypotension in laboratory animals2,3, implicating it as a potential mediator of anaphylactic shock [2].
  • LTD4 hypotension was also reversed by intracerebroventricular (i.c.v.) administration of TRH at a dose that had no effect when given systemically [2].
  • Antagonism of endogenous LTD4 actions, however, was associated with prevention of the NTS-induced fall in SNGFR because of the abrogation of the fall in Kf which characterizes this form of experimental glomerulonephritis [3].
  • Thus, in the autologous phase of PHN, LTD4 mediates glomerular hemodynamic abnormalities and a hemodynamic component of the accompanying proteinuria [4].

Psychiatry related information on leukotriene D4


High impact information on leukotriene D4


Chemical compound and disease context of leukotriene D4


Biological context of leukotriene D4


Anatomical context of leukotriene D4

  • These results demonstrate that the peptido-leukotrienes derived from eicosapentaenoic acid (LTC5 and LTD5) are on the order of five times less potent than the leukotrienes derived from arachidonic acid (LTC4 and LTD4), in terms of increasing the susceptibility of the gastric mucosa to damage and reducing gastric blood flow [19].
  • When displacement of LXA4 binding with pINF114-transfected CHO cells was tested with other eicosanoids, including LXB4, leukotriene D4 (LTD4), LTB4, or prostaglandin E2, only LTD4 competed with LXA4, giving a Ki of 80 nM [20].
  • The observed highly localized protective action of the LTD4 antagonist on the glomerular capillary points to a possibly major functional role for intraglomerularly released LTD4, likely originating from infiltrating leukocytes, in the pathophysiology of this form of glomerulonephritis [3].
  • The synthesis of LTD4 likely occurs directly from macrophages or from macrophage-derived LTA4, through LTC4 synthase in glomerular cells [4].
  • In hepatocytes prepared from untreated rats, this concentration of intracellular LTD4 neither raised intracellular Ca2+ nor activated the conductance [21].

Associations of leukotriene D4 with other chemical compounds


Gene context of leukotriene D4


Analytical, diagnostic and therapeutic context of leukotriene D4


  1. Leukotriene C4 and D4 in neonates with hypoxemia and pulmonary hypertension. Stenmark, K.R., James, S.L., Voelkel, N.F., Toews, W.H., Reeves, J.T., Murphy, R.C. N. Engl. J. Med. (1983) [Pubmed]
  2. Alteration of leukotriene D4 hypotension by thyrotropin releasing hormone. Lux, W.E., Feuerstein, G., Faden, A.I. Nature (1983) [Pubmed]
  3. Preservation of the glomerular capillary ultrafiltration coefficient during rat nephrotoxic serum nephritis by a specific leukotriene D4 receptor antagonist. Badr, K.F., Schreiner, G.F., Wasserman, M., Ichikawa, I. J. Clin. Invest. (1988) [Pubmed]
  4. Leukotriene D4 is a mediator of proteinuria and glomerular hemodynamic abnormalities in passive Heymann nephritis. Katoh, T., Lianos, E.A., Fukunaga, M., Takahashi, K., Badr, K.F. J. Clin. Invest. (1993) [Pubmed]
  5. Effect of leukotriene D4 on ciliary activity in human, guinea-pig and rat respiratory mucosa. Joki, S., Saano, V., Koskela, T., Toskala, E., Bray, M.A., Nuutinen, J. Pulmonary pharmacology. (1996) [Pubmed]
  6. Vasoactive and metabolic effects of leukotriene C4 and D4 in the intestine. Pawlik, W.W., Gustaw, P., Sendur, R., Czarnobilski, K., Konturek, S.J., Beck, G., Jendralla, M. Hepatogastroenterology (1988) [Pubmed]
  7. Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D4-receptor antagonist. Amirav, I., Pawlowski, N. N. Engl. J. Med. (1991) [Pubmed]
  8. Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D4-receptor antagonist. Manning, P.J., Watson, R.M., Margolskee, D.J., Williams, V.C., Schwartz, J.I., O'Byrne, P.M. N. Engl. J. Med. (1990) [Pubmed]
  9. Slow-reacting substances (leukotrienes) contract human airway and pulmonary vascular smooth muscle in vitro. Hanna, C.J., Bach, M.K., Pare, P.D., Schellenberg, R.R. Nature (1981) [Pubmed]
  10. Leukotriene D4: a potent coronary artery vasoconstrictor associated with impaired ventricular contraction. Michelassi, F., Landa, L., Hill, R.D., Lowenstein, E., Watkins, W.D., Petkau, A.J., Zapol, W.M. Science (1982) [Pubmed]
  11. Leukotrienes in acetylcholine-induced contraction of esophageal circular smooth muscle in experimental esophagitis. Kim, N., Sohn, U.D., Mangannan, V., Rich, H., Jain, M.K., Behar, J., Biancani, P. Gastroenterology (1997) [Pubmed]
  12. Leukotriene D4-induced contraction of cat esophageal and lower esophageal sphincter circular smooth muscle. Kim, N., Cao, W., Song, I.S., Kim, C.Y., Sohn, U.D., Harnett, K.M., Biancani, P. Gastroenterology (1998) [Pubmed]
  13. Chemotaxis and transendothelial migration of CD34(+) hematopoietic progenitor cells induced by the inflammatory mediator leukotriene D4 are mediated by the 7-transmembrane receptor CysLT1. Bautz, F., Denzlinger, C., Kanz, L., Möhle, R. Blood (2001) [Pubmed]
  14. Hypoxia and CCl4-induced liver injury, but not acidosis, impair metabolism of cysteinyl leukotrienes in perfused rat liver. Wettstein, M., Gerok, W., Häussinger, D. Hepatology (1990) [Pubmed]
  15. Properties of highly purified leukotriene C4 synthase of guinea pig lung. Yoshimoto, T., Soberman, R.J., Spur, B., Austen, K.F. J. Clin. Invest. (1988) [Pubmed]
  16. Expression of the leukotriene D4 receptor CysLT1, COX-2, and other cell survival factors in colorectal adenocarcinomas. Ohd, J.F., Nielsen, C.K., Campbell, J., Landberg, G., Löfberg, H., Sjölander, A. Gastroenterology (2003) [Pubmed]
  17. The signal transduction system of the leukotriene D4 receptor. Crooke, S.T., Mattern, M., Sarau, H.M., Winkler, J.D., Balcarek, J., Wong, A., Bennett, C.F. Trends Pharmacol. Sci. (1989) [Pubmed]
  18. Characterization of a leukotriene D4 receptor in guinea pig lung. Pong, S.S., DeHaven, R.N. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  19. Comparison of the damage-promoting effects of leukotrienes derived from eicosapentaenoic acid and arachidonic acid on the rat stomach. Wallace, J.L., McKnight, G.W. J. Exp. Med. (1990) [Pubmed]
  20. Identification of a human cDNA encoding a functional high affinity lipoxin A4 receptor. Fiore, S., Maddox, J.F., Perez, H.D., Serhan, C.N. J. Exp. Med. (1994) [Pubmed]
  21. Leukotriene D4 activates a chloride conductance in hepatocytes from lipopolysaccharide-treated rats. Meng, X.J., Carruth, M.W., Weinman, S.A. J. Clin. Invest. (1997) [Pubmed]
  22. Leukotrienes are potent constrictors of human bronchi. Dahlén, S.E., Hedqvist, P., Hammarström, S., Samuelsson, B. Nature (1980) [Pubmed]
  23. Mechanism of action of glucocorticosteroids. Inhibition of T cell proliferation and interleukin 2 production by hydrocortisone is reversed by leukotriene B4. Goodwin, J.S., Atluru, D., Sierakowski, S., Lianos, E.A. J. Clin. Invest. (1986) [Pubmed]
  24. Stimulation by leukotriene D4 of increases in the cytosolic concentration of calcium in dimethylsulfoxide-differentiated HL-60 cells. Baud, L., Goetzl, E.J., Koo, C.H. J. Clin. Invest. (1987) [Pubmed]
  25. Leukotriene D4 mediates survival and proliferation via separate but parallel pathways in the human intestinal epithelial cell line Int 407. Paruchuri, S., Sjölander, A. J. Biol. Chem. (2003) [Pubmed]
  26. CysLT1 receptor upregulation by TGF-beta and IL-13 is associated with bronchial smooth muscle cell proliferation in response to LTD4. Espinosa, K., Bossé, Y., Stankova, J., Rola-Pleszczynski, M. J. Allergy Clin. Immunol. (2003) [Pubmed]
  27. Lipoxygenase metabolism is required for interleukin-3 dependent proliferation and cell cycle progression of the human M-07e cell line. Miller, A.M., Allen, B.S., Ziboh, V. J. Cell. Physiol. (1997) [Pubmed]
  28. Prevention of endogenous leukotriene production during anaphylaxis in the guinea pig by an inhibitor of leukotriene biosynthesis (MK-886) but not by dexamethasone. Guhlmann, A., Keppler, A., Kästner, S., Krieter, H., Brückner, U.B., Messmer, K., Keppler, D. J. Exp. Med. (1989) [Pubmed]
  29. Urinary leukotriene E4 after antigen challenge and in acute asthma and allergic rhinitis. Taylor, G.W., Taylor, I., Black, P., Maltby, N.H., Turner, N., Fuller, R.W., Dollery, C.T. Lancet (1989) [Pubmed]
  30. Angioplasty triggers intracoronary leukotrienes and lipoxin A4. Impact of aspirin therapy. Brezinski, D.A., Nesto, R.W., Serhan, C.N. Circulation (1992) [Pubmed]
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