CYSLTR2
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CYSLTR2
Cysteinyl leukotriene receptor 2, also termed CYSLTR2, is a receptor for cysteinyl leukotrienes (LT) (see leukotrienes#Cysteinyl leukotrienes). CYSLTR2, 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. However, the first discovered receptor for these CsLTs, cysteinyl leukotriene receptor 1 (CysLTR1), appears to play the major role in mediating these reactions. Gene The human gene maps to the long arm of chromosome 13 at position 13q14, a chromosomal region that has long been linked to asthma and other allergic diseases. The gene consists of four exons with all introns located in the genes' 5' UTR region and the entire coding region located in the last exon. CysLTR2'' encodes a protein composed of 347 amino acids and shows only modest similarity to the ''CysLTR1'' gene in that its protein shares only 31% amino acid identity with the CysLTR1 prote ...
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Leukotrienes
Leukotrienes are a family of eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxygenase. Leukotrienes use lipid signaling to convey information to either the cell producing them ( autocrine signaling) or neighboring cells ( paracrine signaling) in order to regulate immune responses. The production of leukotrienes is usually accompanied by the production of histamine and prostaglandins, which also act as inflammatory mediators. One of their roles (specifically, leukotriene D4) is to trigger contractions in the smooth muscles lining the bronchioles; their overproduction is a major cause of inflammation in asthma and allergic rhinitis. Leukotriene antagonists are used to treat these disorders by inhibiting the production or activity of leukotrienes. History and name The name ''leukotriene'', introduced by Swedish biochemist Bengt Sa ...
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LTC4
Leukotriene C4 (LTC4) is a leukotriene. LTC4 has been extensively studied in the context of allergy and asthma. In cells of myeloid origin such as mast cells, its biosynthesis is orchestrated by translocation to the nuclear envelope along with co-localization of cytosolic phospholipase A2 (cPLA2), Arachidonate 5-lipoxygenase (5-LO), 5-lipoxygenase-activating protein (FLAP) and LTC4 synthase (LTC4S), which couples glutathione to an LTA4 intermediate. The MRP1 transporter then secretes cytosolic LTC4 and cell surface proteases further metabolize it by sequential cleavage of the γ-glutamyl and glycine residues off its glutathione segment, generating the more stable products LTD4 and LTE4. All three leukotrienes then bind at different affinities to two G-protein coupled receptors: CYSLTR1 and CYSLTR2, triggering pulmonary vasoconstriction and bronchoconstriction. In cells of non-haematopoietic lineage, endoplasmic reticulum (ER) stress and chemotherapy induce LTC4 biosynthesi ...
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Zafirlukast
Zafirlukast is an orally administered leukotriene receptor antagonist (LTRA) used for the chronic treatment of asthma. While zafirlukast is generally well tolerated, headache and stomach upset often occur. Some rare side effects can occur, which can be life-threatening, such as liver failure. Churg-Strauss syndrome has been associated with zafirlukast, but the relationship isn't thought to be causative in nature. Overdoses of zafirlukast tend to be self-limiting. Zafirlukast, like other LTRAs, works by inhibiting the immune system. Through its action on inflammatory cells in the lungs, zafirlukast reduces the production of inflammatory mediators that are implicated in the pathogenesis of asthma. Zafirlukast is extensively hepatically metabolized by an enzyme called CYP2C9. Zafirlukast inhibits the action of CYP3A4, leading to drug–drug interactions with other drugs that are metabolized by CYP3A4. Genetic differences in LTC4 synthase and CYP2C9 may predict how a person reacts ...
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Montelukast
Montelukast, sold under the brand name Singulair among others, is a medication used in the maintenance treatment of asthma. It is generally less preferred for this use than inhaled corticosteroids. It is not useful for acute asthma attacks. Other uses include allergic rhinitis and hives of long duration. For allergic rhinitis it is a second-line treatment. Common side effects include abdominal pain, cough, and headache. Severe side effects may include allergic reactions, such as anaphylaxis and eosinophilia. Use in pregnancy appears to be safe. Montelukast is in the leukotriene receptor antagonist family of medications. It works by blocking the action of leukotriene D4 in the lungs resulting in decreased inflammation and relaxation of smooth muscle. Montelukast was approved for medical use in the United States in 1998. It is available as a generic medication. In 2020, it was the fourteenth most commonly prescribed medication in the United States, with more than 31million pre ...
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Cysteinyl Leukotriene Receptor 1
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. Gene The human 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. Expression 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, a ...
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Intron
An intron is any Nucleic acid sequence, nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron [i.e., gene] ... must be replaced by that of a transcription unit containing regions which will be lost from the mature messenger – which I suggest we call introns (for intragenic regions) – alternating with regions which will be expressed – exons." (Gilbert 1978) The term ''intron'' refers to both the DNA sequence within a gene and the corresponding RNA sequence in RNA Transcription (genetics), transcripts. The non-intron sequences that become joined by this RNA processing to form the mature RNA are called exons. Introns are found in the genes of most organisms and many viruses and they can be located in both protein-coding genes and genes that function as RNA (noncoding genes). There are four main types of introns: tRN ...
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Gene Polymorphism
A gene is said to be polymorphic if more than one allele occupies that gene's locus within a population. In addition to having more than one allele at a specific locus, each allele must also occur in the population at a rate of at least 1% to generally be considered polymorphic. Gene polymorphisms can occur in any region of the genome. The majority of polymorphisms are silent, meaning they do not alter the function or expression of a gene. Some polymorphisms are visible. For example, in dogs the E locus can have any of five different alleles, known as E, Em, Eg, Eh, and e. Varying combinations of these alleles contribute to the pigmentation and patterns seen in dog coats. A polymorphic variant of a gene can lead to the abnormal expression or to the production of an abnormal form of the protein; this abnormality may cause or be associated with disease. For example, a polymorphic variant of the gene encoding the enzyme CYP4A11, in which thymidine replaces cytosine at the gene's n ...
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Transmission Disequilibrium Test
The transmission disequilibrium test (TDT) was proposed by Spielman, McGinnis and Ewens (1993) as a family-based association test for the presence of genetic linkage between a genetic marker and a trait. It is an application of McNemar's test. A specificity of the TDT is that it will detect genetic linkage only in the presence of genetic association. While genetic association can be caused by population structure, genetic linkage will not be affected, which makes the TDT robust to the presence of population structure. The case of trios: one affected child per family Description of the test We first describe the TDT in the case where families consist of trios (two parents and one affected child). Our description follows the notations used in Spielman, McGinnis & Ewens (1993). The TDT measures the over-transmission of an allele from heterozygous parents to affected offsprings. The ''n'' affected offsprings have 2''n'' parents. These can be represented by the transmitted and ...
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Oligodendrocyte Progenitor Cell
Oligodendrocyte progenitor cells (OPCs), also known as oligodendrocyte precursor cells, NG2-glia, O2A cells, or polydendrocytes, are a subtype of glia in the central nervous system named for their essential role as precursors to oligodendrocytes. They are typically identified by coexpression of PDGFRA and NG2. OPCs play a critical role in developmental and adult myelinogenesis by giving rise to oligodendrocytes, which then ensheath axons and provide electrical insulation in the form of a myelin sheath, enabling faster action potential propagation and high fidelity transmission without a need for an increase in axonal diameter. The loss or lack of OPCs, and consequent lack of differentiated oligodendrocytes, is associated with a loss of myelination and subsequent impairment of neurological functions. In addition, OPCs express receptors for various neurotransmitters and undergo membrane depolarization when they receive synaptic inputs from neurons. Structure OPCs are glial cell ...
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Uracil Nucleotides
Uracil () ( symbol U or Ura) is one of the four nucleobases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by thymine (T). Uracil is a demethylated form of thymine. Uracil is a common and naturally occurring pyrimidine derivative. The name "uracil" was coined in 1885 by the German chemist Robert Behrend, who was attempting to synthesize derivatives of uric acid. Originally discovered in 1900 by Alberto Ascoli, it was isolated by hydrolysis of yeast nuclein; it was also found in bovine thymus and spleen, herring sperm, and wheat germ. It is a planar, unsaturated compound that has the ability to absorb light. Based on 12C/13C isotopic ratios of organic compounds found in the Murchison meteorite, it is believed that uracil, xanthine, and related molecules can also be formed extraterrestrially. Data from the Cassini mission, orbiting in the ...
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GPR17
Uracil nucleotide/cysteinyl leukotriene receptor is a G protein-coupled receptor that in humans is encoded by the ''GPR17'' gene located on chromosome 2 at position q21. The actual activating ligands for and some functions of this receptor are disputed. History Initially discovered in 1998 as an Orphan receptor, i.e. a receptor whose activating ligand(s) and function were unknown, GPR17 was "deorphanized" in a study that reported it to be a receptor for LTC4, LTD4, and uracil nucleotides. In consequence, GPR17 attracted attention as a potential mediator of reactions caused by LTC4 and LTD4 viz., asthma, rhinitis, and urticarial triggered by allergens, nonsteroidal anti-inflammatory drugs, and exercise (see Aspirin-induced asthma). Subsequent reports, however, have varied in results: studies focusing on the allergen and non-allergen reactions find that GPR17-bearing cells do not respond to LTC4, LTD4, and uracil nucleotides while studies focusing on nerve tissue find that certain ...
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GPR99
2-Oxoglutarate receptor 1 (OXGR1), also known as cysteinyl leukotriene receptor E (CysLTE) and GPR99, is a protein that in humans is encoded by the (also termed ''GPR99'') gene. The Gene has recently been nominated as a receptor not only for 2-oxogluterate (see alpha-Ketoglutaric acid) but also for the three cysteinyl leukotrienes (CysLTs), particularly leukotriene E4 (LTE4) and to far lesser extents LTC4 and LTE4. Recent studies implicate GPR99 as a cellular receptor which is activated by LTE4 thereby causing these cells to contribute to mediating various allergic and hypersensitivity responses. History In 2001, a gene projected to code for a G protein-like receptor protein was reported; the gene's apparent protein product was classified as an orphan receptor (i.e., a receptor whose activating ligand and function were unknown) and named ''GPR80''. The projected amino acid sequence of the protein encoded by the ''GPR80'' gene bore similarities to a purinergic receptor, P2Y1, an ...
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