Leukotriene Receptors: State of the Art
- 139 Downloads
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).
KeywordsAirway Smooth Muscle Cell Vascular Smooth Muscle Cell Proliferation Human Airway Smooth Muscle Human Airway Smooth Muscle Cell CysLT Receptor
Unable to display preview. Download preview PDF.
- 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.PubMedCrossRefGoogle 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.PubMedGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedGoogle Scholar