srs a


Summary: A group of LEUKOTRIENES; (LTC4; LTD4; and LTE4) that is the major mediator of BRONCHOCONSTRICTION; HYPERSENSITIVITY; and other allergic reactions. Earlier studies described a "slow-reacting substance of ANAPHYLAXIS" released from lung by cobra venom or after anaphylactic shock. The relationship between SRS-A leukotrienes was established by UV which showed the presence of the conjugated triene. (From Merck Index, 11th ed)

Top Publications

  1. Kelly L, Undem B, Adams G. Antigen-induced contraction of guinea pig isolated pulmonary arteries and lung parenchyma. J Appl Physiol (1985). 1993;74:1563-9 pubmed
    ..These results suggest that both histamine and sulfidopeptide LTs mediate antigen-induced contraction of PA, whereas sulfidopeptide LTs, but not histamine, are involved in the parenchymal response. ..
  2. Abraham W, Ahmed A, Cortes A, Sielczak M, Hallmon J. The effects of a cysteinyl leukotriene antagonist (ONO-1078) on antigen-induced responses in allergic sheep. Prostaglandins Leukot Essent Fatty Acids. 1993;48:233-9 pubmed
    ..4-fold (p < 0.05). Treatment however, did not affect BAL cell numbers or differential.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  3. Heise C, O Dowd B, Figueroa D, Sawyer N, Nguyen T, Im D, et al. Characterization of the human cysteinyl leukotriene 2 receptor. J Biol Chem. 2000;275:30531-6 pubmed
  4. Sheng W, Li C, Zhang W, Yuan Y, Hu H, Fang S, et al. Distinct roles of CysLT1 and CysLT2 receptors in oxygen glucose deprivation-induced PC12 cell death. Biochem Biophys Res Commun. 2006;346:19-25 pubmed
    ..Thus, CysLT(1) and CysLT(2) receptors play distinct roles in OGD-induced PC12 cell death; CysLT(1) attenuates while CysLT(2) facilitates the cell death. ..
  5. Delorme D, Foster A, Girard Y, Rokach J. Synthesis of beta-oxidation products as potential leukotriene metabolites and their detection in bile of anesthetized rat. Prostaglandins. 1988;36:291-302 pubmed
    ..The presence of these metabolites indicates that peptide leukotrienes undergo N-acetylation followed by omega and subsequent beta-oxidation in the anesthetized rat. ..
  6. Konturek S, Brzozowski T, Drozdowicz D, Beck G. Role of leukotrienes in acute gastric lesions induced by ethanol, taurocholate, aspirin, platelet-activating factor and stress in rats. Dig Dis Sci. 1988;33:806-13 pubmed
    ..This study provides evidence that LTC4 is involved in the formation of acute gastric damage and the antagonism of LTC4 may protect the mucosa against various ulcerogens. ..
  7. van Haeringen N, Verbey N, Van Delft J. Antagonists and inhibitors of lipid mediators in experimental inflammation of the cornea. J Ocul Pharmacol. 1993;9:365-72 pubmed
    ..Prophylactic topical treatment with the poly-unsaturated fatty acids eicosapentaenoic acid and columbinic acid or a dietary supplement with fish oil showed less symptoms of keratitis in all respects. ..
  8. Bruijnzeel P, Virchow J, Rihs S, Walker C, Verhagen J. Lack of increased numbers of low-density eosinophils in the circulation of asthmatic individuals. Clin Exp Allergy. 1993;23:261-9 pubmed
    ..This could mean that LTC4 formation is a more sensitive parameter for cell activation than density distribution or cell surface marker expression. ..
  9. Thompson M, Storm van s Gravesande K, Galczenski H, Burnham W, Siminovitch K, Zamel N, et al. A cysteinyl leukotriene 2 receptor variant is associated with atopy in the population of Tristan da Cunha. Pharmacogenetics. 2003;13:641-9 pubmed
    ..0015). This represents the first association of a coding mutation in the CysLT2 receptor gene, located on chromosome 13q14, with the atopic phenotype found in the Tristan da Cunha population. ..

More Information


  1. Zschauer A, Matthews E, Richardson B. Effect of leukotriene C4 on electromechanical activity and Ca2+ uptake in taenia coli. Am J Physiol. 1988;255:C433-41 pubmed
    ..It is concluded that the contractile effects of LTC4 in guinea pig taenia coli occur as a consequence of its ability to open voltage-sensitive Ca2+ channels, an effect that may occur independently of membrane depolarization. ..
  2. Buckle D, Foster K, Taylor J, Tedder J, Thody V, Webster R, et al. Novel 1H-benzimidazol-4-ols with potent 5-lipoxygenase inhibitory activity. J Med Chem. 1987;30:2216-21 pubmed
    ..Standard lipoxygenase inhibitors such as phenidone, BW 755C, and AA 861 were inactive in this system. ..
  3. Ezra D, Laurindo F, Czaja J, Snyder F, Goldstein R, Feuerstein G. Cardiac and coronary consequences of intracoronary platelet activating factor infusion in the domestic pig. Prostaglandins. 1987;34:41-57 pubmed
    ..These data suggest that PAF might play a detrimental role on the coronary circulation and cardiac function, primarily through thromboxane A2 mediated mechanism. ..
  4. Trevethick M, Clayton N, Bahl A, Strong P, Harman I. Leukotrienes do not contribute to the pathogenesis of indomethacin-induced ulceration of the gastric antrum in the re-fed rat. Agents Actions. 1994;41:179-83 pubmed
  5. Yamaguchi T, Mukaiyama O, Itoh K, Satoh Y, Terada A, Iizuka Y. Effects of CS-518, a thromboxane synthase inhibitor, on the asthmatic response. Eur J Pharmacol. 1993;236:43-50 pubmed
  6. Sampson A, Pizzichini E, Bisgaard H. Effects of cysteinyl leukotrienes and leukotriene receptor antagonists on markers of inflammation. J Allergy Clin Immunol. 2003;111:S49-59; discussion S59-61 pubmed
    ..Nitric oxide is also a surrogate marker of asthma and reflects airway inflammation. The anti-inflammatory effects of the leukotriene receptor antagonists and the markers of their activity continue to grow. ..
  7. Stenke L, Mansour M, Reizenstein P, Lindgren J. Stimulation of human myelopoiesis by leukotrienes B4 and C4: interactions with granulocyte-macrophage colony-stimulating factor. Blood. 1993;81:352-6 pubmed
    ..The results suggest that both LTB4 and LTC4 possess strong and specific synergistic stimulatory effects on GM-CSF-induced human myeloid progenitor cell growth. ..
  8. Tagari P, Becker A, Brideau C, Frenette R, Sadl V, Thomas E, et al. Leukotriene generation and metabolism in dogs: inhibition of biosynthesis by MK-0591. J Pharmacol Exp Ther. 1993;265:416-25 pubmed
  9. Hardy G, Stanke Labesque F, Peoc h M, Hakim A, Devillier P, Caron F, et al. Cysteinyl leukotrienes modulate angiotensin II constrictor effects on aortas from streptozotocin-induced diabetic rats. Arterioscler Thromb Vasc Biol. 2001;21:1751-8 pubmed
  10. Sundqvist T, Axelsson K. The cGMP modulator, LY83583 alters oxygen metabolites differently in cultured endothelial cells and isolated neutrophilic granulocytes. Pharmacol Toxicol. 1993;72:169-74 pubmed
    ..The consumption of NADPH in endothelial cells could also cause reduced scavenger functions of the glutathion system, resulting in a further increase in H2O2 release. ..
  11. Arakawa H, Kawikova I, Skoogh B, Hayes J, Morikawa A, Lofdahl C, et al. Role of arachidonic acid metabolites in airway responses induced by trimellitic anhydride in actively sensitized guinea pigs. Am Rev Respir Dis. 1993;147:1116-21 pubmed
    ..Indomethacin, OKY-046 and ketanserin did not significantly affect the extravasation of dye into the airway tissue.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  12. Okuda M, Watase T, Mezawa A, Liu C. The role of leukotriene D4 in allergic rhinitis. Ann Allergy. 1988;60:537-40 pubmed
    ..LTD4 was approximately 5,000 times stronger than histamine in threshold concentration for nasal response. In conclusion, LTD4 plays an important role in nasal allergy presumably through long lasting and strong nasal blockage effects. ..
  13. Ahmed T, Weichman B, Wasserman M, Muccitelli R, Tucker S, Marchette B. Prevention and reversal of endotoxin-induced pulmonary hypertension by a leukotriene antagonist. Eur Respir J. 1988;1:145-52 pubmed
    ..Discontinuation of FPL-57231 was followed by an exaggerated response of PVR during phase II to an average of 209% of baseline (range = 186-235%).(ABSTRACT TRUNCATED AT 250 WORDS) ..
  14. Hisayama T, Takayanagi I, Nakazato F, Hirano K. Epithelium selectively controls hypersensitization of the response of smooth muscle to leukotriene D4 by endogenous prostanoid(s) in guinea-pig trachea. Naunyn Schmiedebergs Arch Pharmacol. 1988;337:296-300 pubmed
    ..These results suggest that epithelium diminishes the sensitizing effect of intramural excitatory PG(s) on responsiveness of tracheal smooth muscle to LTD4, possible via a non-prostanoid substance(s). ..
  15. Ayala L, Choudry N, Fuller R. LTD4-induced bronchoconstriction in patients with asthma: lack of a vagal reflex. Br J Clin Pharmacol. 1988;26:110-2 pubmed
    ..8 mg) showed significant effect on LTD4-induced bronchoconstriction in asthmatic subjects. These results suggest that in asthmatics LTD4-induced bronchoconstriction is unlikely to involve vagal reflexes. ..
  16. Lonigro A, Sprague R, Stephenson A, Dahms T. Relationship of leukotriene C4 and D4 to hypoxic pulmonary vasoconstriction in dogs. J Appl Physiol (1985). 1988;64:2538-43 pubmed
    ..05) and 112 +/- 31% (P less than 0.05), respectively. These results, therefore, do not support the contention that leukotrienes mediate hypoxic pulmonary vasoconstriction in dogs. ..
  17. Carlson R, O Neill Davis L, Chang J. Pharmacologic modulation of PAF-induced mortality in mice. Agents Actions. 1987;21:379-81 pubmed
    ..Therefore, our pharmacological data do not consistently support the notion that PAF-induced lethality is due unequivocally to leukotrienes derived from 5-lipoxygenase metabolism. ..
  18. Katsura K, Minamisawa H, Katayama Y, Shimizu J, Goto T, Urushiyama K, et al. Plasma levels of leukotriene C4, B4, slow reacting substance of anaphylaxis in chronological phases of cerebrovascular disease. Prostaglandins. 1988;36:655-65 pubmed
    ..In patients with cerebral hemorrhage, significant increases in LTB4 were measured in days 1-7 only. These results suggest a clinical relationship between the plasma levels of LT's and cerebrovascular disease. ..
  19. Anwar A, Moqbel R, Walsh G, Kay A, Wardlaw A. Adhesion to fibronectin prolongs eosinophil survival. J Exp Med. 1993;177:839-43 pubmed
  20. Sladek K, Szczeklik A. Cysteinyl leukotrienes overproduction and mast cell activation in aspirin-provoked bronchospasm in asthma. Eur Respir J. 1993;6:391-9 pubmed
    ..abstract truncated at 250 words) ..
  21. Jones S, Adamson S, Bishai I, Lees J, Engelberts D, Coceani F. Eicosanoids in third ventricular cerebrospinal fluid of fetal and newborn sheep. Am J Physiol. 1993;264:R135-42 pubmed
    ..In contrast, CSF thromboxane B2 (n = 2) and total peptidoleukotriene content (n = 4) showed little change during labor or after birth.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  22. Gresele P, Ribaldi E, Mezzasoma A, Quero E, Stasi M, Prosdocimi M, et al. Cloricromene inhibits leukotriene formation by human polymorphonuclear leucocytes by suppressing arachidonate release from membrane phospholipids. Biochem Pharmacol. 1993;45:123-30 pubmed
  23. Nabe T, Kohno S, Tanpo T, Saeki Y, Yamamura H, Horiba M, et al. Inhibitory effect of ONO-1078 on specific binding of peptide leukotrienes to human lung crude membrane. Prostaglandins Leukot Essent Fatty Acids. 1994;51:163-71 pubmed
    ..From these results, it is suggested that ONO-1078 is a highly potent LTD4 antagonist which is expected to be very effective on bronchial asthma. ..
  24. Ashida Y, Nomura M, Kuriki H, Maki Y. The effect of inhaled leukotriene D4, histamine, or antigen on central and peripheral airways of guinea pigs: analysis of bronchograms with an interactive image analysis system. Eur J Pharmacol. 1987;141:299-304 pubmed
  25. Abraham W, Ahmed A, Cortes A, Spinella M, Malik A, Andersen T. A specific endothelin-1 antagonist blocks inhaled endothelin-1-induced bronchoconstriction in sheep. J Appl Physiol (1985). 1993;74:2537-42 pubmed
    ..Thus inhaled ET-1 and, to a lesser extent, ET-3 cause concentration-dependent bronchoconstriction in conscious sheep.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  26. Liu S, Hu H, Gao C, Gao N, Wang G, Wang X, et al. Actions of cysteinyl leukotrienes in the enteric nervous system of guinea-pig stomach and small intestine. Eur J Pharmacol. 2003;459:27-39 pubmed
    ..The receptor mediating these effects was distinct from currently recognized cysteinyl leukotriene receptor subtypes (CysLT(1) and CysLT(2) receptors) and may represent a new receptor subtype. ..
  27. Goerig M, Habenicht A, Zeh W, Salbach P, Kommerell B, Rothe D, et al. Evidence for coordinate, selective regulation of eicosanoid synthesis in platelet-derived growth factor-stimulated 3T3 fibroblasts and in HL-60 cells induced to differentiate into macrophages or neutrophils. J Biol Chem. 1988;263:19384-91 pubmed
  28. Winkler J, Sarau H, Foley J, Crooke S. Phorbol 12-myristate 13-acetate inhibition of leukotriene D4-induced signal transduction was rapidly reversed by staurosporine. Biochem Biophys Res Commun. 1988;157:521-9 pubmed
    ..These data describe cells which have a novel response to phorbol 12-myristate 13-acetate in that the inhibition of leukotriene D4 signal transduction is persistent and yet rapidly reversed by staurosporine. ..
  29. Kim C, Koh J, Han T, Kim D, Kim B, Koh Y. Increased levels of BAL cysteinyl leukotrienesinacute [corrected] RSV bronchiolitis. Acta Paediatr. 2006;95:479-85 pubmed
    ..Among bronchiolitis subjects, high CysLT producers could be distinguished from low CysLT producers by the presence of eosinophilia in BAL fluids, suggesting a pathophysiological heterogeneity in RSV bronchiolitis. ..
  30. Diener M, Scharrer E. The leukotriene D4 receptor blocker, SK&F 104353, inhibits volume regulation in isolated crypts from the rat distal colon. Eur J Pharmacol. 1993;238:217-22 pubmed
    ..These results are in accordance with the hypothesis that leukotriene D4 acts as mediator for the activation of basolateral Cl- channels in the rat colonic epithelium during regulatory decrease in volume. ..
  31. Prins B, Hu R, Nazario B, Pedram A, Frank H, Weber M, et al. Prostaglandin E2 and prostacyclin inhibit the production and secretion of endothelin from cultured endothelial cells. J Biol Chem. 1994;269:11938-44 pubmed
    ..We propose that the vasodilator action of the PGs results, in part, from their ability to inhibit the production of this potent vasoconstrictor. ..
  32. Mahauthaman R, Howell C, Spur B, Youlten L, Clark T, Lessof M, et al. The generation and cellular distribution of leukotriene C4 in human eosinophils stimulated by unopsonized zymosan and glucan particles. J Allergy Clin Immunol. 1988;81:696-705 pubmed
    ..This suggests that zymosan may induce leukotriene generation in the human EOS through a glucan recognition mechanism. ..
  33. Ogletree M, Snapper J, Brigham K. Direct and indirect effects of leukotriene D4 on the lungs of unanesthetized sheep. Respiration. 1987;51:256-65 pubmed
    ..The response of unanesthetized sheep to LTD4 is mediated, at least in part, indirectly by stimulation of the cyclooxygenase pathway of arachidonate metabolism. ..
  34. Hammerbeck D, Brown D. Neurally mediated actions of leukotrienes on ion transport in guinea pig distal colon. J Pharmacol Exp Ther. 1993;264:384-90 pubmed
    ..The results suggest that LTC4 and D4 evoke anion secretion by acting through distinct LT receptor populations. These effects are mediated in part by cholinergic and adrenergic submucosal neurons as well as by colonic prostanoids. ..
  35. Katoh T, Lianos E, Fukunaga M, Takahashi K, Badr K. Leukotriene D4 is a mediator of proteinuria and glomerular hemodynamic abnormalities in passive Heymann nephritis. J Clin Invest. 1993;91:1507-15 pubmed
    ..The synthesis of LTD4 likely occurs directly from macrophages or from macrophage-derived LTA4, through LTC4 synthase in glomerular cells. ..
  36. Foegh M, Hartmann D, Rowles J, Khirabadi B, Alijani M, Helfrich G, et al. Leukotrienes, thromboxane, and platelet activating factor in organ transplantation. Adv Prostaglandin Thromboxane Leukot Res. 1987;17A:140-6 pubmed
    ..In addition, these drugs exert synergistic effect with CsA and azathioprine. ..
  37. Pavia D, Lopez Vidriero M, Clarke S. Mediators and mucociliary clearance in asthma. Bull Eur Physiopathol Respir. 1987;23 Suppl 10:89s-94s pubmed
    ..Some pharmacological agents, used for the relief of bronchospasm and control of asthma, also stimulate mucociliary transport, a desirable additional effect. ..
  38. Edenius C, Heidvall K, Lindgren J. Novel transcellular interaction: conversion of granulocyte-derived leukotriene A4 to cysteinyl-containing leukotrienes by human platelets. Eur J Biochem. 1988;178:81-6 pubmed
    ..After preincubation of platelets with [35S]cysteine, 35S-labeled leukotriene C4 was produced by A23187-stimulated platelet-granulocyte suspensions, strongly indicating a transcellular biosynthesis of this compound. ..
  39. Braun D, Ahn M, Harris J, Chu E, Casey L, Wilbanks G, et al. Sensitivity of tumoricidal function in macrophages from different anatomical sites of cancer patients to modulation of arachidonic acid metabolism. Cancer Res. 1993;53:3362-8 pubmed
    ..Thus, eicosanoids, particularly those of the cyclooxygenase pathway, can be a critical immunoregulatory feature of certain tumor microenvironments. ..
  40. Hartupee D, Passmore J, Jimenez A. Effect of leukotrienes of renal water excretion. Prostaglandins Leukot Essent Fatty Acids. 1993;48:297-303 pubmed
    ..Our experiments suggest that renal LT can decrease urine osmolality and increase urine flow rate and may play a role in renal water excretion. ..
  41. Selig W, Patterson C, Rhoades R. Cyclooxygenase metabolites contribute to oleic acid-induced lung edema by a pressure effect. Exp Lung Res. 1987;13:69-82 pubmed
    ..These data indicate that OA-induced edema formation was greatly amplified by arachidonic acid mediated pressure increases. ..
  42. Skoglund G. Selective inhibition by H7 and staurosporin of phorbol ester responses in U-937 cells. Cell Signal. 1993;5:325-30 pubmed
    ..In addition, the data indicate that selective pharmacological interference with different protein kinase C-mediated processes is achievable. ..
  43. Kleha J, Devesly P, Johns A. Endothelium derived relaxing factor release from canine coronary artery by leukocytes. Can J Physiol Pharmacol. 1995;73:404-8 pubmed
    ..It is suggested that HL-60, THP-1, and DAUDI cells interact with a specific receptor on the endothelial cell and as a result of this interaction the endothelial cells are stimulated to release EDRF. ..
  44. Austen K. Doing what I like. Annu Rev Immunol. 2008;26:1-28 pubmed
    ..My commentary notes some of the highlights for each area of interest and the mentors, collaborators, and trainees whose counsel has been immensely important at particular intervals or over an extended period. ..
  45. Wong C, Thong Y, Seow W. Comparative effects of tetrandrine and berbamine on guineapig airway microvascular leakage induced by platelet-activating factor and other allergic mediators. Int J Immunopharmacol. 1993;15:185-93 pubmed
    ..These results indicate that tetrandrine has broad-spectrum inhibitory activity on allergic mediators, and may have value for the therapy of diseases in which these mediators have a role in pathogenesis. ..
  46. Tong J, Edmunds L. Role of cyclic GMP in the mediation of circadian rhythmicity of the adenylate cyclase-cyclic AMP-phosphodiesterase system in Euglena. Biochem Pharmacol. 1993;45:2087-91 pubmed
    ..These findings suggest that cGMP may serve as an upstream effector that mediates the cAMP oscillation by regulation of the AC-cAMP-PDE system...
  47. Wallace J, Morris G, Beck P, Williamson T, Gingras G. Effects of sucralfate on gastric prostaglandin and leukotriene synthesis: relationship to protective actions. Can J Physiol Pharmacol. 1988;66:666-70 pubmed
    ..The present study supports the hypothesis that prostaglandins do not mediate the protection afforded by exposure to sucralfate. ..
  48. Tajima K, Tokuyama K, Morikawa A, Mochizuki H, Kuroume T. Two cases of aspirin-intolerant asthma whose leukocytes demonstrated hypersensitivity to sulpyrin. Ann Allergy. 1989;62:190-3 pubmed
    ..In those intolerant patients, preincubation of polymorphonuclear leukocytes with sulpyrin enhanced the calcium ionophore A23187-induced leukotriene C4 production as compared with those of healthy adults and aspirin-tolerant asthma. ..
  49. Peskar B, Dreyling K, May B, Schaarschmidt K, Goebell H. Possible mode of action of 5-aminosalicylic acid. Dig Dis Sci. 1987;32:51S-56S pubmed
    ..7 and 1.0 mmol/liter, respectively) without reducing synthesis of LTB4 or sulfidopeptide-LT.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  50. Fujiwara H, Kurihara N, Ohta -, Hirata K, Matsushita H, Kanazawa H, et al. Effect of a new leukotriene receptor antagonist, ONO-1078, on human bronchial smooth muscle in vitro. Prostaglandins Leukot Essent Fatty Acids. 1993;48:241-6 pubmed
    ..The present findings demonstrate that ONO-1078 is a potent antagonist of exogenous and endogenous LT in the human airway. The selective LT antagonist such as ONO-1078 may be valuable in the therapy of allergic asthma. ..
  51. Gulbins E, Schlottmann K, Rauterberg E, Steinhausen M. Effects of rC5a on the circulation of normal and split hydronephrotic rat kidneys. Am J Physiol. 1993;265:F96-103 pubmed
    ..The exact localization of renovascular rC5a effects was performed on the model of the split hydronephrotic rat kidney.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  52. Kanaoka Y, Boyce J. Cysteinyl leukotrienes and their receptors: cellular distribution and function in immune and inflammatory responses. J Immunol. 2004;173:1503-10 pubmed
  53. Ball H, Cook J, Spicer K, Hsu C, Halushka P. Oleic acid-induced pulmonary injury in rats: potential role of sulfidopeptide leukotrienes. Circ Shock. 1988;26:59-70 pubmed
    ..Furthermore, they suggest that the prevention of elevated pulmonary vascular permeability and edema may be necessary, but are clearly not sufficient to prevent arterial hypoxemia following oleic acid injury in the rat. ..