To characterize the influences of leukotriene D4 on regional vascular smooth muscle, effects of leukotriene D4 on vasomotor tone of canine renal and superior mesenteric arterial rings were determined. Vascular smooth muscle tone was measured with isometric force transducers. After tone had been induced with norepinephrine, leukotriene D4, in concentrations of 10(-8) M to 10(-7) M, produced dose-dependent relaxation of renal and superior mesenteric arterial rings. Leukotriene D4-induced relaxation was observed only in those ring preparations in which care had been taken to avoid damaging the luminal surface. Acetylcholine (10(-7) M) also decreased tone in these same ring segments. Neither acetylcholine nor leukotriene D4 altered tone of arterial rings after the endothelium had been intentionally disrupted by rubbing with a cotton-tipped applicator. Nitroglycerin (10(-6) M) relaxed rings both before and after rubbing the intimal surface. These results demonstrate that leukotriene D4 possesses the ...
article{a0090b47-94ce-453b-9412-f151ac7d6530, abstract = {The intestinal epithelial barrier, which is regulated by the actin cytoskeleton, exhibits permeability changes during inflammation. Here we show that activation of the CysLT(1) receptor by the inflammatory mediator leukotriene D-4 (LTD4) causes a rapid increase in stress-fibre formation in intestinal epithelial cells. This effect was mimicked by cytotoxic necrotising factor-1 (CNF-1)-induced activation of RhoA, overexpression of constitutively active RhoA (L63-RhoA) and phorbol-ester-induced activation of protein kinase C (PKC). In accordance, inhibition of RhoA, by C3 exoenzyme or by dominant-negative RhoA (N19-RhoA), as well as GF109203X-induced inhibition of PKC, suppressed the LTD4-induced stress-fibre formation. Introduction of the dominant-negative regulatory domain of PKCdelta, but not the corresponding structures from PKCalpha, betaII or epsilon, blocked the LTD4-induced stress-fibre formation. Evaluating the relationship between ...
The regulation of CD11b integrin levels on human blood leukocytes and leukotriene B4-stimulated skin by a specific leukotriene B4 receptor antagonist (LY293111 ...
Leukotriene D4 (LTD4) is one of the leukotrienes. Its main function in the body is to induce the contraction of smooth muscle, resulting in bronchoconstriction and vasoconstriction. It also increases vascular permeability. LTD-4 is released by basophils. Other leukotrienes that function in a similar manner are leukotrienes C4 and E4. Pharmacological agents that inhibit the function of these leukotrienes are leukotriene receptor antagonists (e.g. Zafirlukast, montelukast) and are useful for asthmatic individuals ...
Receptor desensitization is a universal mechanism to turn off a biological response; in this process, the ability of a physiological trigger to activate a cell is lost despite the continued presence of the stimulus. Receptor desensitization of G-protein-coupled receptors involves uncoupling of the receptor from its G-protein or second-messenger pathway followed by receptor internalization. G-protein-coupled cysteinyl leukotriene type I (CysLT1) receptors regulate immune-cell function and CysLT1 receptors are an established therapeutic target for allergies, including asthma. Desensitization of CysLT1 receptors arises predominantly from protein-kinase-C-dependent phosphorylation of three serine residues in the receptor carboxy terminus. Physiological concentrations of the receptor agonist leukotriene C(4) (LTC(4)) evoke repetitive cytoplasmic Ca(2+) oscillations, reflecting regenerative Ca(2+) release from stores, which is sustained by Ca(2+) entry through store-operated calcium-release-activated calcium
Accepted name: leukotriene-C4 hydrolase. Reaction: leukotriene C4 + H2O = leukotriene D4 + L-glutamate. Other name(s): γ-glutamyl leukotrienase; GGT5. Comments: The mouse enzyme is specific for leukotriene C4, while the human enzyme also has considerable activity towards glutathione and oxidized glutathione (cf. EC 3.4.19.13, glutathione hydrolase) [3-4].. Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: References:. 1. Carter, B.Z., Wiseman, A.L., Orkiszewski, R., Ballard, K.D., Ou, C.N. and Lieberman, M.W. Metabolism of leukotriene C4 in γ-glutamyl transpeptidase-deficient mice. J. Biol. Chem. 272 (1997) 12305-12310. [PMID: 9139674]. 2. Shi, Z.Z., Han, B., Habib, G.M., Matzuk, M.M. and Lieberman, M.W. Disruption of γ-glutamyl leukotrienase results in disruption of leukotriene D4 synthesis in vivo and attenuation of the acute inflammatory response. Mol. Cell Biol. 21 (2001) 5389-5395. [PMID: 11463821]. 3. Han, B., Luo, G., Shi, Z.Z., Barrios, R., Atwood, D., Liu, ...
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【調査レポート】Cipla Ltd (CIPLA):製薬・医療:M&Aディール及び事業提携情報 | 発行日:2018年11月 | 商品コード:DATA904C9882 | 発行/調査会社:GlobalData | Cipla Ltd (CIPLA) - Pharmaceuticals & Healthcare - Deals and Alliances Profile | キーワード:、製薬・医療、 [マーケットレポート.jp]
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Yoshiyuki Ito, Minoru Hirano, Noriko Umemoto, Liqing Zang, Zhipeng Wang, Takehiko Oka, Yasuhito Shimada, Yuhei Nishimura, Ichiro Kurokawa, Hitoshi Mizutani, Toshio Tanaka
BMB Rep. 2008 Feb 29;41(2):139-45.


Abstract

We cloned and pharmacologically characterized the guinea pig cysteinyl leukotriene (CysLT) 2 receptor (gpCysLT2). gpCysLT2 consists of 317 amino acids with 75.3%, 75.2%, 73.3% identity to those of humans, mice and rats, respectively. The gpCysLT2 gene is highly expressed in the lung, moderately in eosinophils, skin, spleen, stomach, colon, and modestly in the small intestine. CysLTs accelerated the proliferation of gpCysLT2-expressing HEK293. Leukotriene C4 (LTC4) and Leukotriene D4 (LTD4) enhanced the cell proliferation higher than Bay-u9773, a CysLT2 selective partial agonist and a nonselective antagonist for CysLT receptors. Bay-u9773 did not antagonize the cell proliferation by LTC4 and LTD4. Despite the equipotency of the mitogenic effect
Leukotrienes (LTs) exist as two distinct classes, hydroxyacids (such as LTB4), and cysteinyl leukotrienes (such as LTC4, LTD4 and LTE4). Leukotriene receptors have been classified into BLT and CysLT types to signify this basic level of selectivity, but there is also heterogeneity within both classes. Thus, there are two subtypes of both BLT, termed BLT1 and BLT2, and CysLT, termed CysLT1 and CysLT2. There may also be further subdivision of CysLT receptors, but this remains to be confirmed. The classification into types and subtypes of LT receptor was based initially on functional data, using the natural agonists and a wide range of antagonists. While LTB4 may be regarded as a selective agonist at BLT receptors, and cysteinyl LTs are selective agonists at CysLT receptors, no subtype-selective agonist has been reported for BLT1 or either CysLT receptor. Furthermore, despite the availability of a plethora of antagonists at both BLT receptors and CysLT1 receptors, no selective antagonist has yet ...
phdthesis{6b9b0641-bb61-4659-a399-f7e79a96bd44, abstract = {Inflammation is a response to injury or pathogen invasion. A large proportion of the bodies immune system is centred in the gastrointestinal tract (GI). Prolonged inflammatory conditions of the GI have been suggested to increase the risk for developing colon cancer. The cysteinyl leukotrienes (CysLTs), LTC4, LTD4 and LTE4 are inflammatory mediators that can bind to four known receptors, two of which are the CysLT1R and CysLT2R. Inhibitors of the CysLT1R are currently used in the clinic as asthma medication. LTD4 has been shown to induce cell proliferation, survival and migration in intestinal epithelial cells (Int407) via the CysLT1R. These mechanisms are often used by cancer cells to surive and spread. Furthermore, increased expression of the CysLT1R in colon cancer patient material is correlated with a poorer survival prognosis. Conversley, increased expression of the CysLT2R is correlated with a better survival prognosis. The aim of ...
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Selectively inhibit the cysteinyl leukotriene receptor, increased activity of which is involved in airway oedema and bronchial smooth muscle constriction.. ...
The presence of specific leukotriene B4 (LTB4) binding sites was investigated in membranes prepared from mouse, rat, guinea pig and rabbit brain. Specific binding sites have been found in guinea pig brain membranes (GPBM) but not in the other species studied. Specific binding of LTB4 to GPBM was proportional to membrane concentration, saturable and reversible, reaching a steady-state suggesting equilibrium after 30 min of incubation. Analysis of the binding data showed a single binding site with a Kd = 2.27 +/- 0.55 nM and a Bmax = 576 +/- 89.6 fmol/mg protein. The relative potencies of LTB4 analogs to displace the tritiated ligand were LTB4 greater than 20-hydroxy-LTB4 much greater than 20-carboxy-LTB4 greater than 12-(S)hydroxy-5,8,10,14(Z,Z,E,Z)-eicosatetraenoic acid; LTD4 and LTC4 did not displace the ligand in concentrations up to 50 microM. The binding was inhibited by monovalent cations and GTP[gamma S] and increased by divalent cations. Specific binding was associated to the cerebral ...
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Chugai Pharmaceutical Co., Ltd. takes great care over the information presented on this website, but it does not guarantee its accuracy, completeness, usefulness, etc. Furthermore, Chugai Pharmaceutical Co., Ltd. will not be responsible for any damages resulting from the use of this website or the information presented on this website. For further details, please read the following "Terms and Conditions of Website Use.". ...
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Cysteinyl leukotriene receptor 1, also termed CYSLTR1, is a receptor for cysteinyl leukotrienes (LT) (see leukotrienes#Cysteinyl leukotrienes). CYSLTR1, by binding these cysteinyl LTs (CysLTs; viz, LTC4, LTD4, and to a much lesser extent, LTE4) contributes to mediating various allergic and hypersensitivity reactions in humans as well as models of the reactions in other animals. The human CysLTR1 gene maps to the X chromosome at position Xq13-Xq21, contains three exons with the entire open reading frame located in exon 3, and codes for a protein composed of 337 amino acids. The CYSLTR1 gene promoter region is distanced from 665 to 30 bp upstream of its transcription start site. CYSLTR1 mRNA is expressed in lung smooth muscle, lung macrophages, monocytes, eosinophils, basophils, neutrophils, platelets, T cells, B lymphocytes, pluripotent hematopoietic stem cells (CD34+), mast cells, pancreas, small intestine, prostate, interstitial cells of the nasal mucosa, airway smooth muscle cells, bronchial ...
... ,LTs,SRS-A,SRS,Leukotriene A4,Leukotriene A4,(2S,3S)-3-(1E,3E,5Z,8Z)-1,3,5,8-Tetradecatetraenyloxiranebutanoic acid,leukotriene A,LTA4,Leukotriene B4,Leukotriene B4,(5S,6Z,8E,10E,12R,14Z)-5,12-Dihydroxy-6,8,10,14-eicosatetraenoic acid,leukotriene B,LTB4,Leukotriene C4,Leukotriene C4,L-gamma-Glutamyl-S-[(1R,2E,4E,6Z,9Z)-1-[(1S)-4-carboxy-1-hydroxybutyl]-2,4,6,9-pentadecatetraenyl]-L-cysteinylglycine,leukotriene C,leukotriene C1,LTC4,Leukotriene D4,Leukotriene D4,S-[(1R,2E,4E,6Z,9Z)-1-[(1S)-4-Carboxy-1-hydroxybutyl]-2,4,6,9-pentadecatetraenyl]-L-cysteinylglycine,leukotriene D,LTD4,Leukotriene E4,Leukotriene E4,(5S,6R,7E,9E,11Z,14Z)-6-[[(2R)-2-Amino-2-carboxyethyl]thio]-5-hydroxy-7,9,11,14-eicosatetraenoic acid,leukotriene E,LTE4
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There has been a considerable increase in our understanding of the role of arachidonic acid metabolites in asthma over the last decade. Arachidonic acid provides a source for both leukotrienes and prostanoids which have a diverse range of properties that are important in regulating the airway inflammatory response. It is clear that cysteinyl leukotrienes are important pro-inflammatory mediators in asthma which act to enhance bronchoconstriction. This has led to the development of a number of agents which either target the enzymes involved in leukotriene synthesis or are antagonists at specific leukotriene receptors. The development of these agents has allowed the role of leukotrienes in different variants of asthma to be studied. The other arm of arachidonic acid metabolism is the cyclo-oxygenase pathway. Cyclo-oxygenase exists in two forms-a constitutive form, COX-1, responsible for the production of housekeeping prostaglandins, and an inducible form, COX-2, which is involved in inflammatory ...
The distribution of [3H]leukotriene D4 [( 3H]LTD4) receptors in subcellular membrane fractions obtained from sheep tracheal smooth muscle was studied. Using differential centrifugation and discontinuous sucrose density gradient centrifugation, the subcellular membranes were separated into six fractions. The [3H]LTD4 receptor distribution profile in these fractions correlated with markers for the plasma membrane (5-nucleotidase and alkaline phosphodiesterase) and did not correlate with markers for the mitochondria (cytochrome c oxidase and succinate-dependent cytochrome c reductase). The dissociation constant (Kd) and maximum number of binding sites (Bmax) for [3H]LTD4 binding to the receptors in the crude mixture of membranes (PII) were 0.38 +/- 0.2 nM and 77 +/- 14 fmol/mg of protein, respectively. The Kd and Bmax of [3H]LTD4 binding to the receptors in the plasma membrane-enriched fraction (FII) were 0.40 +/- 0.2 nM and 268 +/- 46 fmol/mg of protein, respectively. The specificity profile of ...
Synonyms for Cysteinyl in Free Thesaurus. Antonyms for Cysteinyl. 2 words related to cysteine: amino acid, aminoalkanoic acid. What are synonyms for Cysteinyl?
ICI 198615 is a novel, potent and selective peptide leukotriene antagonist. ICI 198,615 may be useful for the the treatment of allergic diseases.
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Western blotting analysis showing the protein expression of CysLT1 and P2Y6 receptors in 16HBE14o- cells.The expression of CysLT1 (44 kDa) and P2Y6 (41 kDa) rec
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