Skip to main content

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 525))

Abstract

The leukotrienes (cysLTs) are lipid mediators derived from the ubiquitous membrane component arachidonic acid. The plethora of biological activities suggested that they activate different receptors. A number of elegant genetic and biochemical studies have been performed to elucidate the nature of these receptors. Results from classical pharmacological and molecular studies indicate that there are two main classes of leukotriene receptors. One based on the biological activities of leukotriene B4 and related hydroxyacids, referred to as BLT receptors, and a second class identified by the cysteinyl- leukotrienes (cysLTs). Activation of the BLT receptors initially was shown to produce potent chemotactic activities on leukocytes whereas the latter class (CysLT receptors) stimulated smooth muscle as well as other cells. Furthermore, there is now sufficient information from classical pharmacological and biochemical assays as well as molecular investigations to divide both categories into receptor sub-classes, namely, BLT1 and BLT2 as well as CysLT1 and CysLT2 (Table 1).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Baker SR, Boot JR, Jamieson WB, Osborne DJ, Sweatman WJF. The comparative in vitro pharmacology of leukotriene D4 and its isomers. Biochem Biophys Res Commun 1981; 103: 1258–64.

    Article  PubMed  CAS  Google Scholar 

  2. Norman P, Abram TS, Cuthbert NJ, Gardiner PJ. The inhibition of [3H]leukotriene D4 binding to guinea-pig lung membranes. The correlation of binding affinity with activity on the guinea-pig ileum. Eur J Pharmacol 1990; 182: 301–12.

    Article  PubMed  CAS  Google Scholar 

  3. Walch L, Norel X, Bäck M, Gascard J-P, Dahlén S-E, Brink C. Pharmacological evidence for cysteinyl-leukotriene receptor subtypes in human pulmonary artery muscle. Br J Pharmacol 2002; 137: 1339–45.

    Article  PubMed  CAS  Google Scholar 

  4. Yokomizo T, Izumi T, Chang K, Takuwa Y, Shimizu T. A G-protein-coupled receptor for leukotriene B4 that mediates Chemotaxis. Nature 1997; 387: 620–4.

    Article  PubMed  CAS  Google Scholar 

  5. Yokomizo T, Kato K, Terawaki K, Izumi T, Shimizu T. A second leukotriene B(4) receptor, BLT2. A new therapeutic target in inflammation and immunological disorders. J Exp Med 2000; 192: 421–32.

    Article  PubMed  CAS  Google Scholar 

  6. Lynch KR, O’Neill GP, Liu Q, Im DS, Sawyer N, Metters KM, Coulombe N, Abramovitz M, Figueroa DJ, Zeng Z, Connolly BM, Bai C, Austin CP, Chateauneuf A, Stocco R, Greig GM, Kargman S, Hooks SB, Hosfield E, Williams DL, Jr. Ford-Hutchinson AW, Caskey CT, Evans JF, Characterization of the human cysteinyl leukotriene CysLTl receptor. Nature 1999; 399: 789–93.

    Article  PubMed  CAS  Google Scholar 

  7. Sarau HM, Ames RS, Chambers J, Ellis C, Elshourbagy N, Foley JJ, Schmidt DB, Muccitelli RM, Jenkins O, Murdock PR, Herrity NC, Halsey W, Sathe G, Muir AI, Nuthulaganti P, Dytko GM, Buckley PT, Wilson S, Bergsma DJ, Hay DW. Identification, molecular cloning, expression, and characterization of a cysteinyl leukotriene receptor. Mol Pharmacol 1999; 56: 657–63.

    PubMed  CAS  Google Scholar 

  8. Nothacker HP, Wang Z, Zhu Y, Reinscheid RK, Lin SH, Civelli O. Molecular cloning and characterization of a second human cysteinyl leukotriene receptor: discovery of a subtype selective agonist. Mol Pharmacol 2000; 58: 1601–8.

    PubMed  CAS  Google Scholar 

  9. Takasaki J, Kamohara M, Matsumoto M, Saito T, Sugimoto T, Ohishi T, Ishii H, Ota T, Nishikawa T, Kawai Y, Masuho Y, Isogai T, Suzuki Y, Sugano S, Furuichi K. The molecular characterization and tissue distribution of the human cysteinyl leukotriene CysLT(2) receptor. Biochem Biophys Res Commun 2000; 274: 316–22.

    Article  PubMed  CAS  Google Scholar 

  10. Heise CE, O’Dowd BF, Figueroa DJ, Sawyer N, Nguyen T, Im DS, Stocco R, Bellefeuille JN, Abramovitz M, Cheng R, Williams DL, Jr. Zeng Z, Liu Q, Ma L, Clements MK, Coulombe N, Liu Y, Austin CP, George SR, O’Neill GP, Metters KM, Lynch KR, Evans JF. Characterization of the human cysteinyl leukotriene 2 receptor. J Biol Chem 2000; 275: 30531–6.

    Article  PubMed  CAS  Google Scholar 

  11. Buckner CK, Krell RD, Laravuso RB, Coursin DB, Bernstein PR, Will JA. Pharmacological evidence that human intralobar airways do not contain different receptors that mediate contractions to leukotriene C4 and leukotriene D4. J Pharmacol Exp Ther 1986; 237: 558–62.

    PubMed  CAS  Google Scholar 

  12. Tudhope SR, Cuthbert NJ, Abram TS, Jennings MA, Maxey RJ, Thompson AM, Norman P, Gardiner PJ. BAY u9773, a novel antagonist of cysteinyl-leukotrienes with activity against two receptor subtypes. Eur J Pharmacol 1994; 264: 317–23.

    Article  PubMed  CAS  Google Scholar 

  13. Back M, Norel X, Walch L, Gascard J, Mazmanian G, Dahlen S, Brink C. Antagonist resistant contractions of the porcine pulmonary artery by cysteinyl-leukotrienes. Eur J Pharmacol 2000; 401: 381–8.

    Article  PubMed  CAS  Google Scholar 

  14. Bäck M, Norel X, Walch L, Gascard J, de Montpreville V, Dahlen S, Brink C. Prostacyclin modulation of contractions of the human pulmonary artery by cysteinyl-leukotrienes. Eur J Pharmacol 2000; 401: 389–95.

    Article  PubMed  Google Scholar 

  15. Datta YH, Romano M, Jacobson BC, Golan DE, Serhan CN, Ewenstein BM. Peptidoleukotrienes are potent agonists of von Willebrand factor secretion and P-selectin surface expression in human umbilical vein endothelial cells. Circulation 1995; 92: 3304–11.

    Article  PubMed  CAS  Google Scholar 

  16. Panettieri RA, Tan EM, Ciocca V Luttmann MA, Leonard TB, Hay DW. Effects of LTD4 on human airway smooth muscle cell proliferation, matrix expression, and contraction In vitro: differential sensitivity to cysteinyl leukotriene receptor antagonists. Am J Respir Cell Mol Biol 1998; 19: 453–61.

    PubMed  CAS  Google Scholar 

  17. Porreca E, Di Febbo C, Di Sciullo A, Angelucci D, Nasuti M, Vitullo P, Reale M, Conti P, Cuccurullo F, Poggi A. Cysteinyl leukotriene D4 induced vascular smooth muscle cell proliferation: a possible role in myointimal hyperplasiA. Thrombosis and Haemostasis 1996; 76: 99–104.

    PubMed  CAS  Google Scholar 

  18. Mellor E, Austen KF, Boyce JA. Cysteinyl leukotriene and uridine diphosphate induce cytokine generation by human mast cells through an interlukin 4-regulated pathway that is inhibited by leukotriene receptor antagonists. J Exp Med 2002; 195: 583–92.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Brink, C. (2003). Leukotriene Receptors: State of the Art. In: Yazici, Z., Folco, G.C., Drazen, J.M., Nigam, S., Shimizu, T. (eds) Advances in Prostaglandin, Leukotriene, and other Bioactive Lipid Research. Advances in Experimental Medicine and Biology, vol 525. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9194-2_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-9194-2_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4831-3

  • Online ISBN: 978-1-4419-9194-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics