Target type: molecularfunction
Combining with a cysteinyl leukotriene to initiate a change in cell activity. Cysteinyl leukotrienes are leukotrienes that contain a peptide group based on cysteine. [GOC:ai, ISBN:0198506732]
Cysteinyl leukotriene receptors (CysLTRs), also known as leukotriene D4 receptors (LTD4Rs), are G protein-coupled receptors (GPCRs) that mediate the biological effects of cysteinyl leukotrienes (CysLTs), a family of potent lipid mediators involved in inflammatory and allergic responses. CysLTs, including leukotriene D4 (LTD4), leukotriene E4 (LTE4), and leukotriene C4 (LTC4), are produced by various cell types, particularly mast cells, during immune responses and allergic reactions. Upon binding to CysLTRs, CysLTs activate downstream signaling pathways, primarily through the G protein Gq, leading to a cascade of intracellular events, including:
* **Activation of phospholipase C (PLC):** Gq activation stimulates PLC, which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into diacylglycerol (DAG) and inositol trisphosphate (IP3).
* **Calcium release:** IP3 binds to its receptors on the endoplasmic reticulum, triggering the release of calcium ions (Ca2+) into the cytosol.
* **Activation of protein kinase C (PKC):** DAG activates PKC, a serine/threonine kinase involved in various cellular processes.
* **Activation of mitogen-activated protein kinases (MAPKs):** CysLTR activation can also activate MAPK signaling pathways, including ERK, JNK, and p38, leading to the regulation of gene expression and cell proliferation.
These intracellular events culminate in the physiological responses associated with CysLTR activation, including:
* **Bronchoconstriction:** CysLTs are potent bronchoconstrictors, contributing to the airway narrowing and difficulty breathing characteristic of asthma and other respiratory conditions.
* **Vascular permeability:** CysLTs increase vascular permeability, allowing fluid and immune cells to leak into tissues, leading to inflammation and edema.
* **Chemotaxis:** CysLTs attract and activate immune cells, such as neutrophils, eosinophils, and macrophages, to the site of inflammation.
* **Mucus production:** CysLTs stimulate mucus secretion in the airways, contributing to airway obstruction and difficulty breathing.
The CysLTR signaling pathway plays a critical role in the pathogenesis of allergic and inflammatory diseases, including asthma, rhinitis, and atopic dermatitis. Therefore, CysLTR antagonists, such as montelukast and zafirlukast, have become important therapeutic agents for the treatment of these conditions. These antagonists block the binding of CysLTs to their receptors, effectively inhibiting the downstream signaling events and reducing the inflammatory and allergic responses.
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Protein | Definition | Taxonomy |
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Cysteinyl leukotriene receptor 2 | A cysteinyl leukotriene receptor 2 that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q9NS75] | Homo sapiens (human) |
Cysteinyl leukotriene receptor 1 | A cysteinyl leukotriene receptor 1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q9Y271] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
clotrimazole | conazole antifungal drug; imidazole antifungal drug; imidazoles; monochlorobenzenes | antiinfective agent; environmental contaminant; xenobiotic | |
ly 171883 | LY 171883: structure in first source; leukotriene receptor antagonist tomelukast : A member of the class of acetophenones that is 1-phenylethanone substituted at position 2 by a hydroxy group, a propyl group at position 3 and a 4-(1H-tetrazol-5-yl)butoxy group at position 4. A leukotriene antagonist, it exhibits anti-asthmatic activity. | acetophenones; aromatic ether; phenols; tetrazoles | anti-asthmatic drug; leukotriene antagonist |
ono 1078 | pranlukast: SRS-A antagonist; leukotriene D4 receptor antagonist | chromones | |
pf 5901 | alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol: structure given in first source; platelet activating factor antagonist | quinolines | |
ici 204,219 | zafirlukast: a leukotriene D4 receptor antagonist | carbamate ester; indoles; N-sulfonylcarboxamide | anti-asthmatic agent; leukotriene antagonist |
ablukast | |||
zileuton | 1-benzothiophenes; ureas | anti-asthmatic drug; EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor; ferroptosis inhibitor; leukotriene antagonist; non-steroidal anti-inflammatory drug | |
wy 48252 | Wy 48252: leukotriene D4 antagonist | ||
pobilukast | pobilukast: a leukotriene receptor antagonist; an antiasthmatic agent; structure in first source; RN refers to (R-(R*,S*)-isomer | ||
fpl 55712 | FPL 55712: inhibitor of SRS-A and LTC4 and LTD4 receptors | aromatic ketone | |
l 648051 | L 648051: antagonist of leukotriene D4 receptor; structure in first source | ||
sr 2640 | SR 2640: leukotriene D4 and E4 antagonist | quinolines | |
rg 12525 | RG 12525: leukotriene D4 antagonist; structure in first source | ||
diethylstilbestrol | diethylstilbestrol : An olefinic compound that is trans-hex-3-ene in which the hydrogens at positions 3 and 4 have been replaced by p-hydroxyphenyl groups. Diethylstilbestrol: A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed) | olefinic compound; polyphenol | antifungal agent; antineoplastic agent; autophagy inducer; calcium channel blocker; carcinogenic agent; EC 1.1.1.146 (11beta-hydroxysteroid dehydrogenase) inhibitor; EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor; endocrine disruptor; xenoestrogen |
leukotriene c4 | leukotriene C4 : A leukotriene that is (5S,7E,9E,11Z,14Z)-5-hydroxyicosa-7,9,11,14-tetraenoic acid in which a glutathionyl group is attached at position 6 via a sulfide linkage. Leukotriene C4: The conjugation product of LEUKOTRIENE A4 and glutathione. It is the major arachidonic acid metabolite in macrophages and human mast cells as well as in antigen-sensitized lung tissue. It stimulates mucus secretion in the lung, and produces contractions of nonvascular and some VASCULAR SMOOTH MUSCLE. (From Dictionary of Prostaglandins and Related Compounds, 1990) | leukotriene | bronchoconstrictor agent; human metabolite; mouse metabolite |
leukotriene d4 | leukotriene D4 : A leukotriene that is (7E,9E,11Z,14Z)-icosa-7,9,11,14-tetraenoic acid substituted by a hydroxy group at position 5 (5S) and a L-cysteinylglycinyl group at position 6 (6R). Leukotriene D4: One of the biologically active principles of SRS-A. It is generated from LEUKOTRIENE C4 after partial hydrolysis of the peptide chain, i.e., cleavage of the gamma-glutamyl portion. Its biological actions include stimulation of vascular and nonvascular smooth muscle, and increases in vascular permeability. (From Dictionary of Prostaglandins and Related Compounds, 1990) | dipeptide; leukotriene; organic sulfide | bronchoconstrictor agent; human metabolite; mouse metabolite |
leukotriene e4 | leukotriene E4 : A leukotriene that is (7E,9E,11Z,14Z)-icosa-7,9,11,14-tetraenoic acid substituted by a hydroxy group at position 5 (5S) and an L-cystein-S-yl group at position 6 (6R). Leukotriene E4: A biologically active principle of SRS-A that is formed from LEUKOTRIENE D4 via a peptidase reaction that removes the glycine residue. The biological actions of LTE4 are similar to LTC4 and LTD4. (From Dictionary of Prostaglandins and Related Compounds, 1990) | amino dicarboxylic acid; L-cysteine thioether; leukotriene; non-proteinogenic L-alpha-amino acid; secondary alcohol | |
montelukast | montelukast: a leukotriene D4 receptor antagonist | aliphatic sulfide; monocarboxylic acid; quinolines | anti-arrhythmia drug; anti-asthmatic drug; leukotriene antagonist |
l 735821 | L 735821: inhibits KCNQ2 channels | N-acyl-amino acid | |
bay u9773 | BAY u9773: a leukotriene C4 antagonist BAYu9773 : A dicarboxylic acid that is that is (7E,9E,11Z,14Z)-icosa-7,9,11,14-tetraenoic acid substituted by a hydroxy group at position 4S and a (4-carboxyphenyl)sulfanediyl group at 5R. It is a dual cysteinyl leukotriene receptor antagonist that acts at the CysLT1 and CysLT2 receptors (IC50 = 0.44 and 0.30 muM, respectively). | benzoic acids; dicarboxylic acid; organic sulfide; polyunsaturated fatty acid; secondary alcohol | leukotriene antagonist |
l 365260 | L 365260: a CCK-B antagonist; structure given in first source; potent & selective CCK-B & gastrin receptor ligand; L 365260 and L 365346 are (R)- and (S)-stereoisomers, respectively | benzodiazepine | |
sulindac sulfide | sulindac sulfide : An aryl sulfide that is a metabolite of sulindac. A non-steroidal anti-inflammatory drug, which also has anticancer activity. sulindac sulfide: sulfated analog of indomethacin & inhibitor of prostaglandin synthesis in vitro; RN given refers to cpd without isomeric designation; structure given in first source | aryl sulfide; monocarboxylic acid; organofluorine compound | antineoplastic agent; apoptosis inducer; non-steroidal anti-inflammatory drug |
gw 1929 | GW 1929: activates peroxisome proliferator-activated receptor-gamma; structure in first source | benzophenones | |
cp 105696 | CP 105696: a leukotriene B4 receptor antagonist; structure in first source | ||
l 365260 | |||
mk 0571 | |||
montelukast sodium | organic sodium salt | ||
3-(((3-carboxycyclohexyl)amino)carbonyl)-4-(3-(4-(4-phenoxybutoxy)phenyl)propoxy)benzoic acid | organonitrogen compound; organooxygen compound |