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)

A class of cell surface receptors recognized by its pharmacological profile. Sigma receptors were originally considered to be opioid receptors because they bind certain synthetic opioids. However they also interact with a variety of other psychoactive drugs, and their endogenous ligand is not known (although they can react to certain endogenous steroids). Sigma receptors are found in the immune, endocrine, and nervous systems, and in some peripheral tissues.

A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.

A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.

Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).

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.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.

The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.

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.

Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.

An opioid analgesic with actions and uses similar to MORPHINE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1095)

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.

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.

Established cell cultures that have the potential to propagate indefinitely.

Receptors of CLONIDINE and other IMIDAZOLINES. Activity of the ligands was earlier attributed to ADRENERGIC ALPHA-2 RECEPTORS. Endogenous ligands include AGMATINE, imidazoleacetic acid ribotide, and harman.

Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known.

The relationship between the dose of an administered drug and the response of the organism to the drug.

A class of G-protein-coupled receptors that are specific for CANNABINOIDS such as those derived from CANNABIS. They also bind a structurally distinct class of endogenous factors referred to as ENDOCANNABINOIDS. The receptor class may play a role in modulating the release of signaling molecules such as NEUROTRANSMITTERS and CYTOKINES.

A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.

Glycoproteins found on the membrane or surface of cells.

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.

CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.

A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.

The rate dynamics in chemical or physical systems.

Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.

A class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H3 receptors were first recognized as inhibitory autoreceptors on histamine-containing nerve terminals and have since been shown to regulate the release of several neurotransmitters in the central and peripheral nervous systems. (From Biochem Soc Trans 1992 Feb;20(1):122-5)

Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.

The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.

A family of hexahydropyridines.

A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.

Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.

Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.

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.

Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only.

Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.

A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS.

The first mixed agonist-antagonist analgesic to be marketed. It is an agonist at the kappa and sigma opioid receptors and has a weak antagonist action at the mu receptor. (From AMA Drug Evaluations Annual, 1991, p97)

Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.

The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.

Specific sites or molecular structures on cell membranes or in cells with which phencyclidine reacts or to which it binds to elicit the specific response of the cell to phencyclidine. Studies have demonstrated the presence of multiple receptor sites for PCP. These are the PCP/sigma site, which binds both PCP and psychotomimetic opiates but not certain antipsychotics, and the PCP site, which selectively binds PCP analogs.

Benzodiazepinones are a class of psychoactive drugs that bind to the GABA-A receptor and enhance its inhibitory effects, producing anxiolytic, sedative, hypnotic, anticonvulsant, and muscle relaxant properties.

Amides of salicylic acid.

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).

The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.

Drug agonism involving selective binding but reduced effect. This can result in some degree of DRUG ANTAGONISM.

Cytoplasmic proteins that bind certain aryl hydrocarbons, translocate to the nucleus, and activate transcription of particular DNA segments. AH receptors are identified by their high-affinity binding to several carcinogenic or teratogenic environmental chemicals including polycyclic aromatic hydrocarbons found in cigarette smoke and smog, heterocyclic amines found in cooked foods, and halogenated hydrocarbons including dioxins and polychlorinated biphenyls. No endogenous ligand has been identified, but an unknown natural messenger with a role in cell differentiation and development is suspected.

Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.

Inorganic or organic compounds that contain sulfur as an integral part of the molecule.

A membrane-bound tumor necrosis family member found primarily on activated T-LYMPHOCYTES that binds specifically to CD30 ANTIGEN. It may play a role in INFLAMMATION and immune regulation.

A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses.

Proteins prepared by recombinant DNA technology.

Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.

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.

A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.

Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.

Compounds that interact with and stimulate the activity of CANNABINOID RECEPTORS.

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.

A cell line derived from cultured tumor cells.

The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)

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.

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.

Bornanes are a class of bicyclic organic compounds, specifically sesquiterpenes, that contain a bornane skeleton, consisting of a cyclohexane ring fused to a cyclopentane ring, and can be found in various essential oils and plants.

A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES.

A serotonin receptor subtype found at high levels in the BASAL GANGLIA and the frontal cortex. It plays a role as a terminal autoreceptor that regulates the rate of SEROTONIN release from nerve endings. This serotonin receptor subtype is closely related to and has similar drug binding properties as the 5-HT1D RECEPTOR. It is particularly sensitive to the agonist SUMATRIPTAN and may be involved in mediating the drug's antimigraine effect.

Compounds having the cannabinoid structure. They were originally extracted from Cannabis sativa L. The most pharmacologically active constituents are TETRAHYDROCANNABINOL; CANNABINOL; and CANNABIDIOL.

Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.

A subclass of cannabinoid receptor found primarily on immune cells where it may play a role modulating release of CYTOKINES.

A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.

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.

Peptides composed of between two and twelve amino acids.

Monohydroxy derivatives of cyclohexanes that contain the general formula R-C6H11O. They have a camphorlike odor and are used in making soaps, insecticides, germicides, dry cleaning, and plasticizers.

Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS.

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.

'Bicyclo compounds' in medicinal chemistry refer to organic molecules containing two fused rings, where each ring shares two common atoms, creating a topological structure that resembles two overlapping circles or bicycle tires.

Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.

A membrane-bound tumor necrosis family member that is expressed on activated antigen-presenting cells such as B-LYMPHOCYTES and MACROPHAGES. It signals T-LYMPHOCYTES by binding the OX40 RECEPTOR.

Amides composed of unsaturated aliphatic FATTY ACIDS linked with AMINES by an amide bond. They are most prominent in ASTERACEAE; PIPERACEAE; and RUTACEAE; and also found in ARISTOLOCHIACEAE; BRASSICACEAE; CONVOLVULACEAE; EUPHORBIACEAE; MENISPERMACEAE; POACEAE; and SOLANACEAE. They are recognized by their pungent taste and for causing numbing and salivation.

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.

A class of opioid receptors recognized by its pharmacological profile. Delta opioid receptors bind endorphins and enkephalins with approximately equal affinity and have less affinity for dynorphins.

Fatty acid derivatives that have specificity for CANNABINOID RECEPTORS. They are structurally distinct from CANNABINOIDS and were originally discovered as a group of endogenous CANNABINOID RECEPTOR AGONISTS.

A subtype of dopamine D2 receptors that are highly expressed in the LIMBIC SYSTEM of the brain.

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).

A group of AROMATIC HYDROCARBONS that have three rings joined as a triad around a single carbon atom so all three are conjoined, in contrast to a linear arrangement (ANTHRACENES) or angular arrangement (PHENANTHRENES).

A quantitative prediction of the biological, ecotoxicological or pharmaceutical activity of a molecule. It is based upon structure and activity information gathered from a series of similar compounds.

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.

Compounds that inhibit or block the activity of CANNABINOID RECEPTORS.

A family of proteins that were originally identified by their ability to cause NECROSIS of NEOPLASMS. Their necrotic effect on cells is mediated through TUMOR NECROSIS FACTOR RECEPTORS which induce APOPTOSIS.

A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.

The characteristic three-dimensional shape of a molecule.

Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here.

A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.

CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)

The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

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)

An EPIDERMAL GROWTH FACTOR related protein that is found in a variety of tissues including EPITHELIUM, and maternal DECIDUA. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form which binds to the EGF RECEPTOR.

A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.

Drugs that bind to and activate histamine receptors. Although they have been suggested for a variety of clinical applications histamine agonists have so far been more widely used in research than therapeutically.

A drug that is derived from opium, which contains from 0.3-1.5% thebaine depending on its origin. It produces strychnine-like convulsions rather than narcosis. It may be habit-forming and is a controlled substance (opiate) listed in the U.S. Code of Federal Regulations, Title 21 Part 1308.12 (1985). (From Merck Index, 11th ed)

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.

A gonadal stimulant and inducer of ovulation. It is used in the treatment of infertility and amenorrhea, but is thought to be less effective than CLOMIPHENE.

The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.

Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.

A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.

Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.

A chemical by-product that results from burning or incinerating chlorinated industrial chemicals and other hydrocarbons. This compound is considered an environmental toxin, and may pose reproductive, as well as, other health risks for animals and humans.

Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.

The endogenous peptides with opiate-like activity. The three major classes currently recognized are the ENKEPHALINS, the DYNORPHINS, and the ENDORPHINS. Each of these families derives from different precursors, proenkephalin, prodynorphin, and PRO-OPIOMELANOCORTIN, respectively. There are also at least three classes of OPIOID RECEPTORS, but the peptide families do not map to the receptors in a simple way.

Transport proteins that carry specific substances in the blood or across cell membranes.

A class of opioid receptors recognized by its pharmacological profile. Kappa opioid receptors bind dynorphins with a higher affinity than endorphins which are themselves preferred to enkephalins.

Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.

TRANSCRIPTION FACTORS that are activated by ligands and heterodimerize with RETINOID X RECEPTORS and bind to peroxisome proliferator response elements in the promoter regions of target genes.

A group of pyrido-indole compounds. Included are any points of fusion of pyridine with the five-membered ring of indole and any derivatives of these compounds. These are similar to CARBAZOLES which are benzo-indoles.

A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine.

Piperazines are a class of heterocyclic organic compounds containing a seven-membered ring with two nitrogen atoms at positions 1 and 4, often used in pharmaceuticals as smooth muscle relaxants, antipsychotics, antidepressants, and antihistamines, but can also be found as recreational drugs with stimulant and entactogen properties.

Drugs that bind to but do not activate SEROTONIN 5-HT1 RECEPTORS, thereby blocking the actions of SEROTONIN 5-HT1 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more of the specific 5-HT1 receptor subtypes.

Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.

The process by which two molecules of the same chemical composition form a condensation product or polymer.

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.

Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).

Compounds that contain a BENZENE ring fused to a furan ring.

Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.

A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)

Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.

Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.

Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.

A membrane bound member of the TNF superfamily that is expressed on activated B-LYMPHOCYTES; MACROPHAGES; and DENDRITIC CELLS. The ligand is specific for the 4-1BB RECEPTOR and may play a role in inducing the proliferation of activated peripheral blood T-LYMPHOCYTES.

Compounds that selectively bind to and block the activation of ADENOSINE A3 RECEPTORS.

Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.

Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.

A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.

The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES.

Arachidonic acids are polyunsaturated fatty acids, specifically a type of omega-6 fatty acid, that are essential for human nutrition and play crucial roles in various biological processes, including inflammation, immunity, and cell signaling. They serve as precursors to eicosanoids, which are hormone-like substances that mediate a wide range of physiological responses.

Phenomena and pharmaceutics of compounds that bind to the same receptor binding-site as an agonist (DRUG AGONISM) for that receptor but exerts the opposite pharmacological effect.

Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.

Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.

A group of compounds consisting in part of two rings sharing one atom (usually a carbon) in common.

Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.

Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.

A subtype of RETINOIC ACID RECEPTORS that are specific for 9-cis-retinoic acid which function as nuclear TRANSCRIPTION FACTORS that regulate multiple signaling pathways.

Pyrrolidines are saturated, heterocyclic organic compounds containing a five-membered ring with four carbon atoms and one nitrogen atom (NRCH2CH2), commonly found as structural components in various alkaloids and used in the synthesis of pharmaceuticals and other organic materials.

Unstable isotopes of bromine that decay or disintegrate emitting radiation. Br atoms with atomic weights 74-78, 80, and 82-90 are radioactive bromine isotopes.

Antibodies produced by a single clone of cells.

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.

A subclass of G-protein coupled SEROTONIN receptors that couple preferentially to GI-GO G-PROTEINS resulting in decreased intracellular CYCLIC AMP levels.

The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

An activating NK cell lectin-like receptor subfamily that regulates immune responses to INFECTION and NEOPLASMS. Members of this subfamily generally occur as homodimers.

Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.

The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.

Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.

Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes.

Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.

THIAZOLES with two keto oxygens. Members are insulin-sensitizing agents which overcome INSULIN RESISTANCE by activation of the peroxisome proliferator activated receptor gamma (PPAR-gamma).

Adherence of cells to surfaces or to other cells.

A serotonin receptor subtype found widely distributed in peripheral tissues where it mediates the contractile responses of variety of tissues that contain SMOOTH MUSCLE. Selective 5-HT2A receptor antagonists include KETANSERIN. The 5-HT2A subtype is also located in BASAL GANGLIA and CEREBRAL CORTEX of the BRAIN where it mediates the effects of HALLUCINOGENS such as LSD.

Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.

A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.

A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.

Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.

Iodinated hydrocarbons are organic compounds containing carbon and hydrogen atoms, with iodine atoms covalently bonded to them, which are used in medical imaging as radiocontrast agents.

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.

Ethylenediamines are organic compounds containing two amine groups linked by a two-carbon chain, widely used in the manufacture of industrial and pharmaceutical products, including chelating agents and polymerization catalysts, but not typically used as a medication on their own.

Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.

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.

A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.

BENZOIC ACID amides.

The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.

Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.

Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT1 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT1 receptor subtypes.

Drugs used for their effects on serotonergic systems. Among these are drugs that affect serotonin receptors, the life cycle of serotonin, and the survival of serotonergic neurons.

A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)

Elements of limited time intervals, contributing to particular results or situations.

A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring.

Large collections of small molecules (molecular weight about 600 or less), of similar or diverse nature which are used for high-throughput screening analysis of the gene function, protein interaction, cellular processing, biochemical pathways, or other chemical interactions.

Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.

A class of saturated compounds consisting of two rings only, having two or more atoms in common, containing at least one hetero atom, and that take the name of an open chain hydrocarbon containing the same total number of atoms. (From Riguady et al., Nomenclature of Organic Chemistry, 1979, p31)

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.

Inbred BALB/c mice are a strain of laboratory mice that have been selectively bred to be genetically identical to each other, making them useful for scientific research and experiments due to their consistent genetic background and predictable responses to various stimuli or treatments.

Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.

A costimulatory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 RECEPTOR. It is closely-related to CD274 antigen; however, its expression is restricted to DENDRITIC CELLS and activated MACROPHAGES.

Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.

An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.

All of the processes involved in increasing CELL NUMBER including CELL DIVISION.

A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)

The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.

Morpholines are organic compounds containing a morpholine ring, which is a saturated six-membered heterocycle made up of four carbon atoms and two oxygen atoms (OCC1CCO), often used as functional groups in pharmaceuticals, agrochemicals, and materials science due to their versatile chemical properties.

A benzodiazepine with pharmacologic actions similar to those of DIAZEPAM that can cause ANTEROGRADE AMNESIA. Some reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. The United States Government has banned the importation of this drug.

The action of a drug that may affect the activity, metabolism, or toxicity of another drug.

The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.

Proteins in the nucleus or cytoplasm that specifically bind RETINOIC ACID or RETINOL and trigger changes in the behavior of cells. Retinoic acid receptors, like steroid receptors, are ligand-activated transcription regulators. Several types have been recognized.

Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.

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).

Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.

Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.

Sympathetic alpha-adrenergic agonist with actions like PHENYLEPHRINE. It is used as a vasoconstrictor in circulatory failure, asthma, nasal congestion, and glaucoma.

Bicyclic bridged compounds that contain a nitrogen which has three bonds. The nomenclature indicates the number of atoms in each path around the rings, such as [2.2.2] for three equal length paths. Some members are TROPANES and BETA LACTAMS.

A class of cell surface receptors that prefer ADENOSINE to other endogenous PURINES. Purinergic P1 receptors are widespread in the body including the cardiovascular, respiratory, immune, and nervous systems. There are at least two pharmacologically distinguishable types (A1 and A2, or Ri and Ra).

Endogenous compounds and drugs that bind to and activate GABA-B RECEPTORS.

Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.

A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (RECEPTORS, OPIOID, KAPPA) and have been shown to play a role as central nervous system transmitters.