Article Figures & Data
Figures
- Fig. 1.
Biosynthesis and chemical structures of endogenous leukotriene receptor agonists, derived from arachidonic acid. Lipoxin (LX) biosynthesis pathways in humans via 15-LO and 5-LO interaction or 12-LO via 5-LO derived LTA4 are also depicted. In addition, resolvin E1, derived from eicosapentaenoic acid (EPA), may act as a partial BLT1R agonist. GT, glutamyl transferase; HEPE, hydroxyeicosapentaenoic acid; LTA4H, LTA4 hydrolase; TXAS, thromboxane synthase.
- Fig. 2.
Schematic representation of the human BLT1 receptor with the boundaries of each transmembrane, extracellular, and intracellular domain derived from the molecular modeled structure described previously (Basu et al., 2007; Kuniyeda et al., 2007). The amino acid residues involved in the ligand binding are shown in red, whereas residues implicated in receptor signaling are shown in green. The C-tail truncations in the described mutants (see text) are indicated by “stop”.
Tables
- TABLE 1
Leukotriene receptors
For full details, see http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=270&familyId=35 .
Receptor BLT1 BLT2 CysLT1 CysLT2 Amino acids Hs 352 389 337 346 Mm 351 360 339 309 Rn 351 358 352 309 NCBI sequence no. Hs NP_858043 NP_062813 NP_006630 NP_065110 Mm NP_032545 NP_065236 NP_067451 NP_598481 Rn NP_067688 NP_446092 NP_446093 NP_596904 Gene name Hs LTB4R LTB4R2 CYSLTR1 CYSLTR2 Mm Ltb4r1 Ltb4r2 Cysltr1 Cysltr2 Rn Ltb4r Ltb4r2 Cysltr1 Cysltr2 Chromosomal location Hs 14q11.2-q12 14q11.2-q12 Xq13.2-21.1 13q14.12-q21.1 Mm 14 C2 14 C1 X D 14 D2 Rn 15p 13 15p 13 Xq 31 15p 11 Selective ligands —a —a —a —a Nonselective ligands LTB4 LTB4; 12-HHT LTC4; LTD4; LTE4 LTC4; LTD4; LTE4 Selective antagonists U75302; CP-105,696 LY-255,283 Montelukast; zafirlukast; pranlukast CysLT2cpd Nonselective antagonists ONO-4057 ONO-4057 BAY U9773 BAY U9773 Hs, Homo sapiens; Mm, Mus muscularis; Rn, Rattus norvegicus; ONO-4057, (5-[2-(2-carboxyethyl)-3-[6-(4-methoxyphenyl)-5E-hexenyl]oxyphenoxy]valeric acid.
↵a No ligands identified.
Receptor Cytokine Cell Effecta Reference BLT1 IFN-γ Monocytes ↓ mRNA; ↓ protein; ↓ chemotaxis Pettersson et al., 2005 TNF-α Monocytes ↓ mRNA; ↓ protein Pettersson et al., 2005 Granulocytes ↓ protein Pettersson et al., 2003 IL-1β Vascular SMCs ↑ mRNA Bäck et al., 2005 HUVECs ↑ mRNA; ↑ protein Qiu et al., 2006 IL-10 Monocytes ↑ mRNA; ↑ protein Pettersson et al., 2005 LPS Monocytes ↓ mRNA Pettersson et al., 2005 Granulocytes ↓ protein Pettersson et al., 2003 Vascular SMCs ↑ mRNA Bäck et al., 2005 HUVECs ↑ mRNA; ↑ protein; ↑ [Ca2+]i Qiu et al., 2006 IL-5 Eosinophils ↑ chemotaxis Sehmi et al., 1992; Thivierge et al., 2000 ↵a ↑, up-regulation; ↓, down-regulation; specified are the effects (at mRNA, protein, and functional level).
Receptor Cytokine Cell Effecta Reference CysLT1 IL-4 Monocytes and monocytes-derived macrophages ↑ mRNA; ↑; protein; ↑ [Ca2+]i Thivierge et al., 2001 ↑ mRNA Woszczek et al., 2005; Shirasaki et al., 2007 + Anti-CD40 antibody B lymphocytes ↑ mRNA; ↑ protein Early et al., 2007 ↑ [Ca2+]i; ↑ IgE/IgG production Lamoureux et al., 2006 T lymphocytes ↑ mRNA; ↑ protein Early et al., 2007 IL-5 Eosinophil-differentiated HL60 ↑ mRNA; ↑ protein; ↑ [Ca2+]i Thivierge et al., 2000 IL-13 Monocytes and monocyte-derived macrophages ↑ mRNA; ↑ protein; ↑ [Ca2+]i Thivierge et al., 2001 ↑ mRNA Thivierge et al., 2001; Shirasaki et al., 2007 Lung fibroblasts ↑ mRNA; ↑, protein; ↑ eotaxin production Chibana et al., 2003 Airway SMCs No effect on mRNA; ↑ protein; ↑ cell proliferation Espinosa et al., 2003 IFN-γ Airway SMCs ↑ mRNA; ↑ protein; ↑ cell stiffness Amrani et al., 2001 Airway SMCs ↑ mRNA; ↑ protein; no effect on cell proliferation Espinosa et al., 2003 IL-1β HUVECs ↑ mRNA Gronert et al., 2001 TGF-β Airway SMCs No effect on mRNA; ↓ protein; ↓ cell proliferation Espinosa et al., 2003 IL-10 (zymosan-induced) Monocytes and monocyte-derived dendritic cells ↓ mRNA; ↓ [Ca2+]I and chemotaxis Woszczek et al., 2008b ↓ mRNA; ↓ [Ca2+]i and chemotaxis Thivierge et al., 2009 LPS Monocyte-derived dendritic cell ↓ mRNA; ↓ protein; ↓ [Ca2+]i and chemotaxis Thivierge et al., 2006 CysLT2 IL-4 HUVECs ↑ mRNA Lötzer et al., 2003 Mast cells ↑ protein Mellor et al., 2003 B and T lymphocytes, monocytes, eosinophils ↑ mRNA; ↑ protein Early et al., 2007 IL-13 Monocytes ↑ mRNA Shirasaki et al., 2007 IFN-γ Eosinophils (asthmatics) ↑ mRNA; ↑ protein Fujii et al., 2005 ECs ↑ mRNA; ↑ [Ca2+]i Woszczek et al., 2007 Monocytes, T and B lymphocytes ↑ mRNA; ↑ protein Early et al., 2007 IL-18 HUVECs ↑ mRNA; ↑ protein (first 2 h) Zhou et al., 2009 TNF-α HUVECs ↓ mRNA Lötzer et al., 2003; Sjöström et al., 2003 LPS HUVECs ↓ mRNA Sjöström et al., 2003 Monocyte-derived dendritic cell ↑ mRNA; ↑ protein Thivierge et al., 2006 IL-1β HUVECs ↓ mRNA Sjöström et al., 2003 IL-10 Monocytes and monocyte-derived dendritic cells ↓ mRNA Woszczek et al., 2008b ↵a ↑, up-regulation; ↓, down-regulation; specified are the effects (at mRNA, protein, and functional level).
