A trienoic fatty acid that consists of heptadeca-5,8,10-trienoic acid bearing an additional 12-hydroxy substituent.
ChEBI ID: 72783
There is 1 compound belonging to this class, involving 4 study.
Member | Definition | Role |
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12S-HHTrE | A trienoic fatty acid that consists of (5Z,8E,10E)-heptadeca-5,8,10-trienoic acid bearing an additional 12S-hydroxy substituent. |
Pre-1990 | 1990-2000 | 2001-2010 | 2011-2020 | Post-2020 |
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0 | 0 | 1 | 3 | 0 |
Article |
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First Structure-Activity Relationship Study of Potent BLT2 Agonists as Potential Wound-Healing Promoters.
The first potent leukotriene B4 (LTB4) receptor type 2 (BLT2) agonists, endogenous 12( |
Elucidation of Mechanism for Ligand Efficacy at Leukotriene B
G protein-coupled receptors (GPCRs) have always been important drug targets in the pharmaceutical industry. One major question for the current GPCR drug discovery is how drugs have distinct efficacies at the same GPCR target. Related to this question, we studied how different ligands can have disparate efficacies at Leukotriene B |
12(S)-Hydroxyheptadeca-5Z, 8E, 10E-trienoic acid is a natural ligand for leukotriene B4 receptor 2.
Activated blood platelets and macrophages metabolize prostaglandin H(2) into thromboxane A(2) and 12(S)-hydroxyheptadeca-5Z, 8E, 10E-trienoic acid (12-HHT) in an equimolar ratio through the action of thromboxane synthase. Although it has been shown that 12-HHT is abundant in tissues and bodily fluids, this compound has long been viewed as a by-product lacking any specific function. We show that 12-HHT is a natural ligand for leukotriene B(4) (LTB(4)) receptor-2 (BLT2), a G protein-coupled receptor that was originally identified as a low-affinity receptor for LTB(4). BLT2 agonistic activity in lipid fractions from rat small intestine was identified as 12-HHT using high-performance liquid chromatography and mass spectrometry. Exogenously expressed BLT2 in mammalian cells was activated by synthetic 12-HHT, as assessed by guanosine 5'-O-(3-thio) triphosphate binding, the activation of intracellular signaling pathways, and chemotaxis assay. Displacement analysis using [(3)H]LTB(4) showed that 12-HHT binds to BLT2 with a higher affinity than LTB(4). Lipid extracts from cyclooxygenase 1-deficient mice failed to activate BLT2. Bone marrow-derived mast cells (BMMCs) isolated from wild-type mice migrated toward a low concentration of 12-HHT, whereas BMMCs from BLT2-deficient mice did not. We conclude that 12-HHT is a natural lipid agonist of BLT2 in vivo and induces chemotaxis of mast cells. |