An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS).
Cell surface proteins that bind THROMBOXANES with high affinity and trigger intracellular changes influencing the behavior of cells. Some thromboxane receptors act via the inositol phosphate and diacylglycerol second messenger systems.
Receptors, Thromboxane A2, Prostaglandin H2
A subclass of eicosanoid receptors that have specificity for THROMBOXANE A2 and PROSTAGLANDIN H2.
An enzyme found predominantly in platelet microsomes. It catalyzes the conversion of PGG(2) and PGH(2) (prostaglandin endoperoxides) to thromboxane A2. EC 184.108.40.206.
Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Prostaglandin Endoperoxides, Synthetic
Synthetic compounds that are analogs of the naturally occurring prostaglandin endoperoxides and that mimic their pharmacologic and physiologic activities. They are usually more stable than the naturally occurring compounds.
6-Ketoprostaglandin F1 alpha
The physiologically active and stable hydrolysis product of EPOPROSTENOL. Found in nearly all mammalian tissue.
A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. The most frequently encountered member of this group is the prostaglandin H2.
Cell surface receptors that bind prostaglandins with high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin receptor subtypes have been tentatively named according to their relative affinities for the endogenous prostaglandins. They include those which prefer prostaglandin D2 (DP receptors), prostaglandin E2 (EP1, EP2, and EP3 receptors), prostaglandin F2-alpha (FP receptors), and prostacyclin (IP receptors).
A cyclic endoperoxide intermediate produced by the action of CYCLOOXYGENASE on ARACHIDONIC ACID. It is further converted by a series of specific enzymes to the series 2 prostaglandins.
A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).
Precursors in the biosynthesis of prostaglandins and thromboxanes from arachidonic acid. They are physiologically active compounds, having effect on vascular and airway smooth muscles, platelet aggregation, etc.
A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes.
Glycogen Synthase Kinase 3
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
Nitric Oxide Synthase Type I
A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in NERVE TISSUE.
Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor.
A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.
A class of compounds named after and generally derived from C20 fatty acids (EICOSANOIC ACIDS) that includes PROSTAGLANDINS; LEUKOTRIENES; THROMBOXANES, and HYDROXYEICOSATETRAENOIC ACIDS. They have hormone-like effects mediated by specialized receptors (RECEPTORS, EICOSANOID).
Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.
A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.
The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)
An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.
Acrylic acids or acrylates which are substituted in the C-2 position with a methyl group.
2-Octylcyclopentaneheptanoic acids. The family of saturated carbon-20 cyclic fatty acids that represent the parent compounds of the prostaglandins.
Compounds obtained by chemical synthesis that are analogs or derivatives of naturally occurring prostaglandins and that have similar activity.
Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects.
The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.
Compounds that inhibit the action of prostaglandins.
(11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities.
Platelet Aggregation Inhibitors
Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Dose-Response Relationship, Drug
An enzyme that catalyzes the conversion of L-serine and 1-(indol-3-yl)glycerol 3-phosphate to L-tryptophan and glyceraldehyde 3-phosphate. It is a pyridoxal phosphate protein that also catalyzes the conversion of serine and indole into tryptophan and water and of indoleglycerol phosphate into indole and glyceraldehyde phosphate. (From Enzyme Nomenclature, 1992) EC 220.127.116.11.
(9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1-oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9-carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics.
NG-Nitroarginine Methyl Ester
A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.
Amino Acid Oxidoreductases
A series of prostaglandin-like compounds that are produced by the attack of free-radical species on unsaturated fatty acids, especially ARACHIDONIC ACID, of cellular MEMBRANES. Once cleaved from the lipid membrane by the action of phospholipases they can circulate into various bodily fluids and eventually be excreted. Although these compounds resemble enzymatically synthesized prostaglandins their stereoisometric arrangement is usually different than the "naturally occurring" compounds.
Amino Acid Sequence
A group of LEUKOTRIENES; (LTC4; LTD4; and LTE4) that is the major mediator of BRONCHOCONSTRICTION; HYPERSENSITIVITY; and other allergic reactions. Earlier studies described a "slow-reacting substance of ANAPHYLAXIS" released from lung by cobra venom or after anaphylactic shock. The relationship between SRS-A leukotrienes was established by UV which showed the presence of the conjugated triene. (From Merck Index, 11th ed)
Mitochondrial Proton-Translocating ATPases
Proton-translocating ATPases responsible for ADENOSINE TRIPHOSPHATE synthesis in the MITOCHONDRIA. They derive energy from the respiratory chain-driven reactions that develop high concentrations of protons within the intermembranous space of the mitochondria.
Alkyl and Aryl Transferases
Bicyclo Compounds, Heterocyclic
The principal cyclooxygenase metabolite of arachidonic acid. It is released upon activation of mast cells and is also synthesized by alveolar macrophages. Among its many biological actions, the most important are its bronchoconstrictor, platelet-activating-factor-inhibitory, and cytotoxic effects.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
An inhibitor of nitric oxide synthetase which has been shown to prevent glutamate toxicity. Nitroarginine has been experimentally tested for its ability to prevent ammonia toxicity and ammonia-induced alterations in brain energy and ammonia metabolites. (Neurochem Res 1995:200(4):451-6)
Fatty Acid Synthases
Cell surface receptors for EPOPROSTENOL. They are coupled to HETEROTRIMERIC G-PROTEINS.
A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, pre-eclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders.
A competitive inhibitor of nitric oxide synthetase.
Salts of nitrous acid or compounds containing the group NO2-. The inorganic nitrites of the type MNO2 (where M=metal) are all insoluble, except the alkali nitrites. The organic nitrites may be isomeric, but not identical with the corresponding nitro compounds. (Grant & Hackh's Chemical Dictionary, 5th ed)
An enzyme of the transferase class that catalyzes condensation of the succinyl group from succinyl coenzyme A with glycine to form delta-aminolevulinate. It is a pyridoxyal phosphate protein and the reaction occurs in mitochondria as the first step of the heme biosynthetic pathway. The enzyme is a key regulatory enzyme in heme biosynthesis. In liver feedback is inhibited by heme. EC 18.104.22.168.
Cyclooxygenase 2 Inhibitors
A subclass of cyclooxygenase inhibitors with specificity for CYCLOOXYGENASE-2.
Fatty Acids, Unsaturated
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A mitochondrial cytochrome P450 enzyme that catalyzes the 18-hydroxylation of steroids in the presence of molecular oxygen and NADPH-specific flavoprotein. This enzyme, encoded by CYP11B2 gene, is important in the conversion of CORTICOSTERONE to 18-hydroxycorticosterone and the subsequent conversion to ALDOSTERONE.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Rats, Inbred Strains
Multisubunit enzymes that reversibly synthesize ADENOSINE TRIPHOSPHATE. They are coupled to the transport of protons across a membrane.
The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)
ATP Synthetase Complexes
Multisubunit enzyme complexes that synthesize ADENOSINE TRIPHOSPHATE from energy sources such as ions traveling through channels.
Enzymes of the isomerase class that catalyze the oxidation of one part of a molecule with a corresponding reduction of another part of the same molecule. They include enzymes converting aldoses to ketoses (ALDOSE-KETOSE ISOMERASES), enzymes shifting a carbon-carbon double bond (CARBON-CARBON DOUBLE BOND ISOMERASES), and enzymes transposing S-S bonds (SULFUR-SULFUR BOND ISOMERASES). (From Enzyme Nomenclature, 1992) EC 5.3.
A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system.
Platelet Activating Factor
A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.
An eicosanoid, derived from the cyclooxygenase pathway of arachidonic acid metabolism. It is a stable and synthetic analog of EPOPROSTENOL, but with a longer half-life than the parent compound. Its actions are similar to prostacyclin. Iloprost produces vasodilation and inhibits platelet aggregation.
A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.
Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.
Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).
Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)
Isoprostanes derived from the free radical oxidation of ARACHIDONIC ACID. Although similar in structure to enzymatically synthesized prostaglandin F2alpha (DINOPROST), they occur through non-enzymatic oxidation of cell membrane lipids.
Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2.
A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.
The major metabolite in neutrophil polymorphonuclear leukocytes. It stimulates polymorphonuclear cell function (degranulation, formation of oxygen-centered free radicals, arachidonic acid release, and metabolism). (From Dictionary of Prostaglandins and Related Compounds, 1990)
Arteries which arise from the abdominal aorta and distribute to most of the intestines.
Rats, Inbred WKY
A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. Most frequently encountered member of this group is the prostaglandin G2.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
Derivatives of phenylacetic acid. Included under this heading are a variety of acid forms, salts, esters, and amides that contain the benzeneacetic acid structure. Note that this class of compounds should not be confused with derivatives of phenyl acetate, which contain the PHENOL ester of ACETIC ACID.
Transferases (Other Substituted Phosphate Groups)
Nitric Oxide Donors
A diverse group of agents, with unique chemical structures and biochemical requirements, which generate NITRIC OXIDE. These compounds have been used in the treatment of cardiovascular diseases and the management of acute myocardial infarction, acute and chronic congestive heart failure, and surgical control of blood pressure. (Adv Pharmacol 1995;34:361-81)
An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.
Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
The force that opposes the flow of BLOOD through a vascular bed. It is equal to the difference in BLOOD PRESSURE across the vascular bed divided by the CARDIAC OUTPUT.
Anti-Inflammatory Agents, Non-Steroidal
Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.
A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.
A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.
Sequence Homology, Amino Acid
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
The first committed enzyme of the biosynthesis pathway that leads to the production of STEROLS. it catalyzes the synthesis of SQUALENE from farnesyl pyrophosphate via the intermediate PRESQUALENE PYROPHOSPHATE. This enzyme is also a critical branch point enzyme in the biosynthesis of ISOPRENOIDS that is thought to regulate the flux of isoprene intermediates through the sterol pathway.
A lipoxygenase metabolite of ARACHIDONIC ACID. It is a highly selective ligand used to label mu-opioid receptors in both membranes and tissue sections. The 12-S-HETE analog has been reported to augment tumor cell metastatic potential through activation of protein kinase C. (J Pharmacol Exp Ther 1995; 274(3):1545-51; J Natl Cancer Inst 1994; 86(15):1145-51)
Disease Models, Animal
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
21-Amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, ENDOTHELIN-1; ENDOTHELIN-2; and ENDOTHELIN-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides.
Rats, Inbred SHR
A strain of Rattus norvegicus with elevated blood pressure used as a model for studying hypertension and stroke.
Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.
A class of cyclic prostaglandins that contain the 6,9-epoxy bond. Endogenous members of this family are biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES.