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Sphingosine N-Acyltransferase: An enzyme that catalyzes the acyltransferase of SPHINGOSINE to N-acylsphingosine using acyl-COENZYME A as donor and COENZYME A as acceptor. The enzyme is mainly localized in the MITOCHONDRIA.Amines: A group of compounds derived from ammonia by substituting organic radicals for the hydrogens. (From Grant & Hackh's Chemical Dictionary, 5th ed)Azirines: Unsaturated azacyclopropane compounds that are three-membered heterocycles of a nitrogen and two carbon atoms.4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine: A dual inhibitor of both cyclooxygenase and lipoxygenase pathways. It exerts an anti-inflammatory effect by inhibiting the formation of prostaglandins and leukotrienes. The drug also enhances pulmonary hypoxic vasoconstriction and has a protective effect after myocardial ischemia.Salicylanilides: 2-Hydroxy-N-phenylbenzamides. N-phenyl substituted salicylamides. Derivatives have been used as fungicides, anti-mildew agents and topical antifungal agents. In concentrated form may cause irritation of skin and mucous membranes.3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester: A dihydropyridine derivative, which, in contrast to NIFEDIPINE, functions as a calcium channel agonist. The compound facilitates Ca2+ influx through partially activated voltage-dependent Ca2+ channels, thereby causing vasoconstrictor and positive inotropic effects. It is used primarily as a research tool.BenzothiepinsKetonesPteridines: Compounds based on pyrazino[2,3-d]pyrimidine which is a pyrimidine fused to a pyrazine, containing four NITROGEN atoms.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Fluorine Compounds: Inorganic compounds that contain fluorine as an integral part of the molecule.BenzoxepinsHydrocarbons, FluorinatedAmine Oxidase (Copper-Containing): A group of enzymes including those oxidizing primary monoamines, diamines, and histamine. They are copper proteins, and, as their action depends on a carbonyl group, they are sensitive to inhibition by semicarbazide.Biogenic Amines: A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology.Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Oxidoreductases: 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)Leukotriene B4: 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)Ceramides: Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.Chlorofluorocarbons, Methane: A group of methane-based halogenated hydrocarbons containing one or more fluorine and chlorine atoms.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.DiazomethaneOxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Fluoroacetates: Derivatives of acetic acid with one or more fluorines attached. They are almost odorless, difficult to detect chemically, and very stable. The acid itself, as well as the derivatives that are broken down in the body to the acid, are highly toxic substances, behaving as convulsant poisons with a delayed action. (From Miall's Dictionary of Chemistry, 5th ed)2-Propanol: An isomer of 1-PROPANOL. It is a colorless liquid having disinfectant properties. It is used in the manufacture of acetone and its derivatives and as a solvent. Topically, it is used as an antiseptic.Pyrazoles: Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.Neurokinin-1 Receptor Antagonists: Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS.Amphibian Venoms: Venoms produced by frogs, toads, salamanders, etc. The venom glands are usually on the skin of the back and contain cardiotoxic glycosides, cholinolytics, and a number of other bioactive materials, many of which have been characterized. The venoms have been used as arrow poisons and include bufogenin, bufotoxin, bufagin, bufotalin, histrionicotoxins, and pumiliotoxin.Phospholipases A2: Phospholipases that hydrolyze the acyl group attached to the 2-position of PHOSPHOGLYCERIDES.Tyrosinemias: A group of disorders which have in common elevations of tyrosine in the blood and urine secondary to an enzyme deficiency. Type I tyrosinemia features episodic weakness, self-mutilation, hepatic necrosis, renal tubular injury, and seizures and is caused by a deficiency of the enzyme fumarylacetoacetase. Type II tyrosinemia features INTELLECTUAL DISABILITY, painful corneal ulcers, and keratoses of the palms and plantar surfaces and is caused by a deficiency of the enzyme TYROSINE TRANSAMINASE. Type III tyrosinemia features INTELLECTUAL DISABILITY and is caused by a deficiency of the enzyme 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE. (Menkes, Textbook of Child Neurology, 5th ed, pp42-3)Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.Phospholipases A: Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.Absidia: A genus of zygomycetous fungi, family Mucoraceae, order MUCORALES, which sometimes causes infection in humans.Chemistry: A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Spectrophotometry, Ultraviolet: Determination of the spectra of ultraviolet absorption by specific molecules in gases or liquids, for example Cl2, SO2, NO2, CS2, ozone, mercury vapor, and various unsaturated compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Trifluoroacetic Acid: A very strong halogenated derivative of acetic acid. It is used in acid catalyzed reactions, especially those where an ester is cleaved in peptide synthesis.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Indicators and Reagents: Substances used for the detection, identification, analysis, etc. of chemical, biological, or pathologic processes or conditions. Indicators are substances that change in physical appearance, e.g., color, at or approaching the endpoint of a chemical titration, e.g., on the passage between acidity and alkalinity. Reagents are substances used for the detection or determination of another substance by chemical or microscopical means, especially analysis. Types of reagents are precipitants, solvents, oxidizers, reducers, fluxes, and colorimetric reagents. (From Grant & Hackh's Chemical Dictionary, 5th ed, p301, p499)Photoaffinity Labels: Biologically active molecules which are covalently bound to the enzymes or binding proteins normally acting on them. Binding occurs due to activation of the label by ultraviolet light. These labels are used primarily to identify binding sites on proteins.Phenothiazines: Compounds containing dibenzo-1,4-thiazine. Some of them are neuroactive.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Arachidonic AcidsEthersCoumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.Phospholipases A2, Cytosolic: A subcategory of phospholipases A2 that occur in the CYTOSOL.Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride (FLUORIDES) to prevent dental caries.Sulfonamides: A group of compounds that contain the structure SO2NH2.Cyclohexanones: Cyclohexane ring substituted by one or more ketones in any position.Benzoates: Derivatives of BENZOIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxybenzene structure.Pyrones: Keto-pyrans.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Receptors, Neurokinin-1: A class of cell surface receptors for TACHYKININS with a preference for SUBSTANCE P. Neurokinin-1 (NK-1) receptors have been cloned and are members of the G protein coupled receptor superfamily. They are found on many cell types including central and peripheral neurons, smooth muscle cells, acinar cells, endothelial cells, fibroblasts, and immune cells.ThiadiazolesBenzylamines: Toluenes in which one hydrogen of the methyl group is substituted by an amino group. Permitted are any substituents on the benzene ring or the amino group.PhotochemistryQuinolinesPiperidines: A family of hexahydropyridines.Phenyl Ethers: Ethers that are linked to a benzene ring structure.Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Inhibitory Concentration 50: The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture.Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.ThiazolesEstersOxidoreductases, N-DemethylatingMagnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).ThiophenesKinetics: The rate dynamics in chemical or physical systems.Arachidonic Acid: 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.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Affinity Labels: Analogs of those substrates or compounds which bind naturally at the active sites of proteins, enzymes, antibodies, steroids, or physiological receptors. These analogs form a stable covalent bond at the binding site, thereby acting as inhibitors of the proteins or steroids.Cyclooxygenase 1: A constitutively-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes.Naphthalenes: Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.AnilidesCytochrome P-450 CYP2B1: A major cytochrome P-450 enzyme which is inducible by PHENOBARBITAL in both the LIVER and SMALL INTESTINE. It is active in the metabolism of compounds like pentoxyresorufin, TESTOSTERONE, and ANDROSTENEDIONE. This enzyme, encoded by CYP2B1 gene, also mediates the activation of CYCLOPHOSPHAMIDE and IFOSFAMIDE to MUTAGENS.Potassium Channels, Calcium-Activated: Potassium channels whose activation is dependent on intracellular calcium concentrations.Cyclooxygenase Inhibitors: 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.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.Spectrometry, Mass, Electrospray Ionization: A mass spectrometry technique used for analysis of nonvolatile compounds such as proteins and macromolecules. The technique involves preparing electrically charged droplets from analyte molecules dissolved in solvent. The electrically charged droplets enter a vacuum chamber where the solvent is evaporated. Evaporation of solvent reduces the droplet size, thereby increasing the coulombic repulsion within the droplet. As the charged droplets get smaller, the excess charge within them causes them to disintegrate and release analyte molecules. The volatilized analyte molecules are then analyzed by mass spectrometry.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.SulfonesSalicylates: The salts or esters of salicylic acids, or salicylate esters of an organic acid. Some of these have analgesic, antipyretic, and anti-inflammatory activities by inhibiting prostaglandin synthesis.Drug Evaluation, Preclinical: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.Masoprocol: A potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. The compound also inhibits formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase to a lesser extent. It also serves as an antioxidant in fats and oils.Torpedo: A genus of the Torpedinidae family consisting of several species. Members of this family have powerful electric organs and are commonly called electric rays.Lipoxygenase Inhibitors: Compounds that bind to and inhibit that enzymatic activity of LIPOXYGENASES. Included under this category are inhibitors that are specific for lipoxygenase subtypes and act to reduce the production of LEUKOTRIENES.NaphthyridinesImidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Aryl Hydrocarbon Hydroxylases: A large group of cytochrome P-450 (heme-thiolate) monooxygenases that complex with NAD(P)H-FLAVIN OXIDOREDUCTASE in numerous mixed-function oxidations of aromatic compounds. They catalyze hydroxylation of a broad spectrum of substrates and are important in the metabolism of steroids, drugs, and toxins such as PHENOBARBITAL, carcinogens, and insecticides.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Cyclooxygenase 2: An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and INFLAMMATION. It is the target of COX2 INHIBITORS.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.SemicarbazidesPyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Cytochrome P-450 CYP3A: A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.Receptors, Nicotinic: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.Benzimidazoles: Compounds with a BENZENE fused to IMIDAZOLES.Cytochrome P-450 Enzyme System: A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.Octopamine: An alpha-adrenergic sympathomimetic amine, biosynthesized from tyramine in the CNS and platelets and also in invertebrate nervous systems. It is used to treat hypotension and as a cardiotonic. The natural D(-) form is more potent than the L(+) form in producing cardiovascular adrenergic responses. It is also a neurotransmitter in some invertebrates.Receptors, Biogenic Amine: Cell surface proteins that bind biogenic amines with high affinity and regulate intracellular signals which influence the behavior of cells. Biogenic amine is a chemically imprecise term which, by convention, includes the catecholamines epinephrine, norepinephrine, and dopamine, the indoleamine serotonin, the imidazolamine histamine, and compounds closely related to each of these.Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Cross-Linking Reagents: Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Calcium: 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.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Dinoprostone: 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.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.PiperazinesCricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Indomethacin: 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.Oxidoreductases Acting on CH-NH Group Donors: Enzymes catalyzing the dehydrogenation of secondary amines, introducing a C=N double bond as the primary reaction. In some cases this is later hydrolyzed.Prostaglandin-Endoperoxide Synthases: Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor.Iodine Radioisotopes: Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.Heterocyclic Compounds: Ring compounds having atoms other than carbon in their nuclei. (Grant & Hackh's Chemical Dictionary, 5th ed)Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Cell Line, Tumor: A cell line derived from cultured tumor cells.Calcimycin: 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.Phenylhydrazines: Diazo derivatives of aniline, used as a reagent for sugars, ketones, and aldehydes. (Dorland, 28th ed)Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Mice, Inbred C57BLMonoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Actinomycetales: An order of gram-positive, primarily aerobic BACTERIA that tend to form branching filaments.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.Phenethylamines: A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)Phenylacetates: 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.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.MethylaminesCell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Serotonin: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Molecular Weight: The sum of the weight of all the atoms in a molecule.Aniline CompoundsSympathomimetics: Drugs that mimic the effects of stimulating postganglionic adrenergic sympathetic nerves. Included here are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters.IminesEthylaminesDihydroxyphenylalanine: A beta-hydroxylated derivative of phenylalanine. The D-form of dihydroxyphenylalanine has less physiologic activity than the L-form and is commonly used experimentally to determine whether the pharmacological effects of LEVODOPA are stereospecific.Benzene DerivativesPhosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.Carcinogens: Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Cyclization: Changing an open-chain hydrocarbon to a closed ring. (McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Molecular Conformation: The characteristic three-dimensional shape of a molecule.AcridinesSpectrophotometry, Infrared: Spectrophotometry in the infrared region, usually for the purpose of chemical analysis through measurement of absorption spectra associated with rotational and vibrational energy levels of molecules. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Amination: The creation of an amine. It can be produced by the addition of an amino group to an organic compound or reduction of a nitro group.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Monoamine Oxidase Inhibitors: A chemically heterogeneous group of drugs that have in common the ability to block oxidative deamination of naturally occurring monoamines. (From Gilman, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p414)PhenylpropionatesToluidinesButylaminesAmides: Organic compounds containing the -CO-NH2 radical. Amides are derived from acids by replacement of -OH by -NH2 or from ammonia by the replacement of H by an acyl group. (From Grant & Hackh's Chemical Dictionary, 5th ed)Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Reserpine: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.Carbamates: Derivatives of carbamic acid, H2NC(=O)OH. Included under this heading are N-substituted and O-substituted carbamic acids. In general carbamate esters are referred to as urethanes, and polymers that include repeating units of carbamate are referred to as POLYURETHANES. Note however that polyurethanes are derived from the polymerization of ISOCYANATES and the singular term URETHANE refers to the ethyl ester of carbamic acid.PropylaminesNitrosamines: A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties.PolyaminesBenzyl CompoundsGlycosides: Any compound that contains a constituent sugar, in which the hydroxyl group attached to the first carbon is substituted by an alcoholic, phenolic, or other group. They are named specifically for the sugar contained, such as glucoside (glucose), pentoside (pentose), fructoside (fructose), etc. Upon hydrolysis, a sugar and nonsugar component (aglycone) are formed. (From Dorland, 28th ed; From Miall's Dictionary of Chemistry, 5th ed)Cinanserin: A serotonin antagonist with limited antihistaminic, anticholinergic, and immunosuppressive activity.Prodrugs: A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.Vesicular Biogenic Amine Transport Proteins: Integral membrane proteins of the LIPID BILAYER of SECRETORY VESICLES that catalyze transport and storage of biogenic amine NEUROTRANSMITTERS such as ACETYLCHOLINE; SEROTONIN; MELATONIN; HISTAMINE; and CATECHOLAMINES. The transporters exchange vesicular protons for cytoplasmic neurotransmitters.Diamines: Organic chemicals which have two amino groups in an aliphatic chain.Drug Design: The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.Aminobiphenyl Compounds: Biphenyl compounds substituted in any position by one or more amino groups. Permitted are any substituents except fused rings.Dopamine: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.Arylamine N-Acetyltransferase: An enzyme that catalyzes the transfer of acetyl groups from ACETYL-COA to arylamines. It can also catalyze acetyl transfer between arylamines without COENZYME A and has a wide specificity for aromatic amines, including SEROTONIN. However, arylamine N-acetyltransferase should not be confused with the enzyme ARYLALKYLAMINE N-ACETYLTRANSFERASE which is also referred to as SEROTONIN ACETYLTRANSFERASE.Thiourea: A photographic fixative used also in the manufacture of resins. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance may reasonably be anticipated to be a carcinogen (Merck Index, 9th ed). Many of its derivatives are ANTITHYROID AGENTS and/or FREE RADICAL SCAVENGERS.Hydrocarbons, Aromatic: Organic compounds containing carbon and hydrogen in the form of an unsaturated, usually hexagonal ring structure. The compounds can be single ring, or double, triple, or multiple fused rings.Palladium: A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys.Furans: Compounds with a 5-membered ring of four carbons and an oxygen. They are aromatic heterocycles. The reduced form is tetrahydrofuran.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Silanes: Compounds similar to hydrocarbons in which a tetravalent silicon atom replaces the carbon atom. They are very reactive, ignite in air, and form useful derivatives.Metaraminol: A sympathomimetic agent that acts predominantly at alpha-1 adrenergic receptors. It has been used primarily as a vasoconstrictor in the treatment of HYPOTENSION.Phenylethyl Alcohol: An antimicrobial, antiseptic, and disinfectant that is used also as an aromatic essence and preservative in pharmaceutics and perfumery.PhenylbutyratesAlkenes: Unsaturated hydrocarbons of the type Cn-H2n, indicated by the suffix -ene. (Grant & Hackh's Chemical Dictionary, 5th ed, p408)AmidinesTetrahydroisoquinolines: A group of ISOQUINOLINES in which the nitrogen containing ring is protonated. They derive from the non-enzymatic Pictet-Spengler condensation of CATECHOLAMINES with ALDEHYDES.BiguanidesHydrazones: Compounds of the general formula R:N.NR2, as resulting from the action of hydrazines with aldehydes or ketones. (Grant & Hackh's Chemical Dictionary, 5th ed)Amino Alcohols: Compounds possessing both a hydroxyl (-OH) and an amino group (-NH2).Benzylamine Oxidase: An aspect of monoamine oxidase, EC 1.4.3.4. Catalyzes the oxidation of benzylamine to form benzaldehyde, ammonia and hydrogen peroxide.Organometallic Compounds: A class of compounds of the type R-M, where a C atom is joined directly to any other element except H, C, N, O, F, Cl, Br, I, or At. (Grant & Hackh's Chemical Dictionary, 5th ed)