TXA2
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TXA2
Thromboxane A2 (TXA2) is a type of thromboxane that is produced by activated platelets during hemostasis and has prothrombotic properties: it stimulates activation of new platelets as well as increases platelet aggregation. This is achieved by activating the thromboxane receptor, which results in platelet-shape change, inside-out activation of integrins, and degranulation. Circulating fibrinogen binds these receptors on adjacent platelets, further strengthening the clot. Thromboxane A2 is also a known vasoconstrictor and is especially important during tissue injury and inflammation. It is also regarded as responsible for Prinzmetal's angina. Receptors that mediate TXA2 actions are thromboxane A2 receptors. The human TXA2 receptor (TP) is a typical G protein-coupled receptor (GPCR) with seven transmembrane segments. In humans, two TP receptor splice variants – TPα and TPβ – have so far been cloned. Synthesis and breakdown TXA2 is generated from prostaglandin H2 by thrombox ...
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Eicosanoid Synthesis
Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, around 20 carbon units in length. Eicosanoids are a sub-category of oxylipins, i.e. oxidized fatty acids of diverse carbon units in length, and are distinguished from other oxylipins by their overwhelming importance as cell signaling molecules. Eicosanoids function in diverse physiological systems and pathological processes such as: mounting or inhibiting inflammation, allergy, fever and other immune responses; regulating the abortion of pregnancy and normal childbirth; contributing to the perception of pain; regulating cell growth; controlling blood pressure; and modulating the regional flow of blood to tissues. In performing these roles, eicosanoids most often act as autocrine signaling agents to impact their cells of origin or as paracrine signaling agents to impact cells in the proximity of ...
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Thromboxane Receptor
The thromboxane receptor (TP) also known as the prostanoid TP receptor is a protein that in humans is encoded by the ''TBXA2R'' gene, The thromboxane receptor is one among the five classes of prostanoid receptors and was the first eicosanoid receptor cloned. The TP receptor derives its name from its preferred endogenous ligand thromboxane A2. Gene The gene responsible for directing the synthesis of the thromboxane receptor, ''TBXA2R'', is located on chromosome 19 at position p13.3, spans 15 kilobases, and contains 5 exons. ''TBXA2R'' codes for a member of the G protein-coupled super family of seven-transmembrane receptors. Heterogeneity Molecular biology findings have provided definitive evidence for two human TP receptor subtypes. The originally cloned TP from placenta (343 amino acids in length) is known as the α isoform and the splice variant cloned from endothelium (with 407 amino acids), termed the β isoform. The first 328 amino acids are the same for both isoforms, ...
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Platelets
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot. Platelets have no cell nucleus; they are fragments of cytoplasm that are derived from the megakaryocytes of the bone marrow or lung, which then enter the circulation. Platelets are found only in mammals, whereas in other vertebrates (e.g. birds, amphibians), thrombocytes circulate as intact mononuclear cells. One major function of platelets is to contribute to hemostasis: the process of stopping bleeding at the site of interrupted endothelium. They gather at the site and, unless the interruption is physically too large, they plug the hole. First, platelets attach to substances outside the interrupted endothelium: ''adhesion''. Second, they change shape, turn on receptors and secrete chemical messengers: ''activatio ...
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U46619
U46619 is a stable synthetic analog of the endoperoxide prostaglandin PGH2 first prepared in 1975, and acts as a thromboxane A2 (TP) receptor agonist. It potently stimulates TP receptor-mediated, but not other prostaglandin receptor-mediated responses in various in vitro preparations and exhibits many properties similar to thromboxane A2, including shape change and aggregation of platelets and smooth muscle contraction. U46619 is a vasoconstrictor that mimics the hydroosmotic effect of vasopressin Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travel .... References Prostaglandins {{Molecular-biology-stub ...
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Thromboxane B2
Thromboxane B2 is an inactive metabolite/product of thromboxane A2. It is almost completely cleared in the urine. It itself is not involved in platelet activation and aggregation in case of a wound, but its precursor, thromboxane A2, is. Thromboxane A2 synthesis is the target of the drug aspirin, which inhibits the COX-1 enzyme (the source of thromboxane A2 in platelets). 2-(3,4-Di-hydroxyphenyl)-ethanol (DHPE) is a phenolic component of extra-virgin olive oil. An olive oil fraction containing DHPE can inhibit platelet aggregation and thromboxane B2 formation in vitro.Inhibition of platelet aggregation and eicosanoid production by phenolic components of olive oil. Anna Petroni, Milena Blasevich, Marco Salami, Nadia Papini, Gian F. Montedoro and Claudio Gallia, Thrombosis Research Thrombosis Research is an international peer-reviewed medical journal published by Elsevier Elsevier () is a Dutch academic publishing company specializing in scientific, technical, and medical ...
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Cyclooxygenase 1
Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for formation of prostanoids, including thromboxane and prostaglandins such as prostacyclin, from arachidonic acid. A member of the animal-type heme peroxidase family, it is also known as prostaglandin G/H synthase. The specific reaction catalyzed is the conversion from arachidonic acid to prostaglandin H2 via a short-living prostaglandin G2 intermediate. Pharmaceutical inhibition of COX can provide relief from the symptoms of inflammation and pain. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, exert their effects through inhibition of COX. Those that are specific to the COX-2 isozyme are called COX-2 inhibitors. The active metabolite (AM404) of paracetamol is a COX inhibitor, a fact to which some or all of its therapeutic effect has been attributed. In medicine, the root symbol "COX" is ...
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Aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat include Kawasaki disease, pericarditis, and rheumatic fever. Aspirin is also used long-term to help prevent further heart attacks, ischaemic strokes, and blood clots in people at high risk. For pain or fever, effects typically begin within 30 minutes. Aspirin works similarly to other NSAIDs but also suppresses the normal functioning of platelets. One common adverse effect is an upset stomach. More significant side effects include stomach ulcers, stomach bleeding, and worsening asthma. Bleeding risk is greater among those who are older, drink alcohol, take other NSAIDs, or are on other blood thinners. Aspirin is not recommended in the last part of pregnancy. It is not generally recommended in children with infections because of the risk of ...
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12-Hydroxyheptadecatrienoic Acid
1 (one, unit, unity) is a number representing a single or the only entity. 1 is also a numerical digit and represents a single unit of counting or measurement. For example, a line segment of ''unit length'' is a line segment of length 1. In conventions of sign where zero is considered neither positive nor negative, 1 is the first and smallest positive integer. It is also sometimes considered the first of the infinite sequence of natural numbers, followed by  2, although by other definitions 1 is the second natural number, following  0. The fundamental mathematical property of 1 is to be a multiplicative identity, meaning that any number multiplied by 1 equals the same number. Most if not all properties of 1 can be deduced from this. In advanced mathematics, a multiplicative identity is often denoted 1, even if it is not a number. 1 is by convention not considered a prime number; this was not universally accepted until the mid-20th century. Additionally, 1 is ...
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Thromboxane
Thromboxane is a member of the family of lipids known as eicosanoids. The two major thromboxanes are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6-membered ether-containing ring. Thromboxane is named for its role in blood clot formation (thrombosis). Production Thromboxane-A synthase, an enzyme found in platelets, converts the arachidonic acid derivative prostaglandin H2 to thromboxane. Mechanism Thromboxane acts by binding to any of the thromboxane receptors, G-protein-coupled receptors coupled to the G protein Gq. Functions Thromboxane is a vasoconstrictor and a potent hypertensive agent, and it facilitates platelet aggregation. It is in homeostatic balance in the circulatory system with prostacyclin, a related compound. The mechanism of secretion of thromboxanes from platelets is still unclear. They act in the formation of blood clots and reduce blood flow to the site of a clot. If the cap of a vulnerable plaque erodes or rupture ...
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Thromboxane-A Synthase
Thromboxane A synthase 1 (, platelet, cytochrome P450, family 5, subfamily A), also known as TBXAS1, is a cytochrome P450 enzyme that, in humans, is encoded by the ''TBXAS1'' gene. Function This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity. This endoplasmic reticulum membrane protein catalyzes the conversion of prostaglandin H2 to thromboxane A2, a potent vasoconstrictor and inducer of platelet aggregation, and also to 12-Hydroxyheptadecatrienoic acid (i.e. 12-(''S'')-hydroxy-5''Z'',8''E'',10''E''-heptadecatrienoic acid or 12-HHT) an agonist of Leukotriene B4 receptors (i.e. BLT2 receptors) and mediator of certain BLT2 receptor actions. The enz ...
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