GABA Agonists: Endogenous compounds and drugs that bind to and activate GAMMA-AMINOBUTYRIC ACID receptors (RECEPTORS, GABA).GABA Antagonists: Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.GABA Agents: Substances used for their pharmacological actions on GABAergic systems. GABAergic agents include agonists, antagonists, degradation or uptake inhibitors, depleters, precursors, and modulators of receptor function.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.Chromatography, Affinity: A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)GABA Modulators: Substances that do not act as agonists or antagonists but do affect the GAMMA-AMINOBUTYRIC ACID receptor-ionophore complex. GABA-A receptors (RECEPTORS, GABA-A) appear to have at least three allosteric sites at which modulators act: a site at which BENZODIAZEPINES act by increasing the opening frequency of GAMMA-AMINOBUTYRIC ACID-activated chloride channels; a site at which BARBITURATES act to prolong the duration of channel opening; and a site at which some steroids may act. GENERAL ANESTHETICS probably act at least partly by potentiating GABAergic responses, but they are not included here.Receptors, GABA-A: 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.GABA Plasma Membrane Transport Proteins: A family of plasma membrane neurotransmitter transporter proteins that regulates extracellular levels of the inhibitory neurotransmitter GAMMA-AMINOBUTYRIC ACID. They differ from GABA RECEPTORS, which signal cellular responses to GAMMA-AMINOBUTYRIC ACID. They control GABA reuptake into PRESYNAPTIC TERMINALS in the CENTRAL NERVOUS SYSTEM through high-affinity sodium-dependent transport.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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Kinetics: The rate dynamics in chemical or physical systems.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.Binding, Competitive: 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.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.Receptors, GABA-B: A subset of GABA RECEPTORS that signal through their interaction with HETEROTRIMERIC G-PROTEINS.Antibody Affinity: A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes.GABA Uptake Inhibitors: Compounds that suppress or block the plasma membrane transport of GAMMA-AMINOBUTYRIC ACID by GABA PLASMA MEMBRANE TRANSPORT PROTEINS.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.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)GABA-A Receptor Agonists: Endogenous compounds and drugs that bind to and activate GABA-A RECEPTORS.Recombinant Proteins: Proteins prepared by recombinant DNA technology.GABA-A Receptor Antagonists: Drugs that bind to but do not activate GABA-A RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-A RECEPTOR AGONISTS.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).Muscimol: A neurotoxic isoxazole isolated from species of AMANITA. It is obtained by decarboxylation of IBOTENIC ACID. Muscimol is a potent agonist of GABA-A RECEPTORS and is used mainly as an experimental tool in animal and tissue studies.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Baclofen: A GAMMA-AMINOBUTYRIC ACID derivative that is a specific agonist of GABA-B RECEPTORS. It is used in the treatment of MUSCLE SPASTICITY, especially that due to SPINAL CORD INJURIES. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Bicuculline: An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.Nipecotic AcidsStructure-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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Protein Structure, Tertiary: 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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.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).Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.GABA-B Receptor Agonists: Endogenous compounds and drugs that bind to and activate GABA-B RECEPTORS.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Receptors, Cell Surface: 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.Picrotoxin: A noncompetitive antagonist at GABA-A receptors and thus a convulsant. Picrotoxin blocks the GAMMA-AMINOBUTYRIC ACID-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates.Phosphinic Acids: Inorganic or organic derivatives of phosphinic acid, H2PO(OH). They include phosphinates and phosphinic acid esters.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.4-Aminobutyrate Transaminase: An enzyme that converts brain gamma-aminobutyric acid (GAMMA-AMINOBUTYRIC ACID) into succinate semialdehyde, which can be converted to succinic acid and enter the citric acid cycle. It also acts on beta-alanine. EC 2.6.1.19.Recombinant Fusion Proteins: 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.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.GABA-B Receptor Antagonists: Drugs that bind to but do not activate GABA-B RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-B RECEPTOR AGONISTS.Neural Inhibition: The function of opposing or restraining the excitation of neurons or their target excitable cells.Mutation: 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.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.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.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.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.Peptides: 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.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.CHO Cells: 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.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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Molecular Weight: The sum of the weight of all the atoms in a molecule.Glutamate Decarboxylase: A pyridoxal-phosphate protein that catalyzes the alpha-decarboxylation of L-glutamic acid to form gamma-aminobutyric acid and carbon dioxide. The enzyme is found in bacteria and in invertebrate and vertebrate nervous systems. It is the rate-limiting enzyme in determining GAMMA-AMINOBUTYRIC ACID levels in normal nervous tissues. The brain enzyme also acts on L-cysteate, L-cysteine sulfinate, and L-aspartate. EC 4.1.1.15.Escherichia coli: 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.PyridazinesPeptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.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.Diazepam: 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.Transfection: 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.Protein Subunits: Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.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.Inhibitory Postsynaptic Potentials: Hyperpolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during NEUROTRANSMISSION. They are local changes which diminish responsiveness to excitatory signals.Brain: 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.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.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)Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.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.Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.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.Membrane Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.Peptide Library: A collection of cloned peptides, or chemically synthesized peptides, frequently consisting of all possible combinations of amino acids making up an n-amino acid peptide.Protein Structure, Secondary: 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.Benzodiazepines: A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring.Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.Allosteric Regulation: 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.Spectrometry, Fluorescence: Measurement of the intensity and quality of fluorescence.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Xenopus laevis: The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).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.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.Flunitrazepam: 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.Adenosine Triphosphate: 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.Vigabatrin: An analogue of GAMMA-AMINOBUTYRIC ACID. It is an irreversible inhibitor of 4-AMINOBUTYRATE TRANSAMINASE, the enzyme responsible for the catabolism of GAMMA-AMINOBUTYRIC ACID. (From Martindale The Extra Pharmacopoeia, 31st ed)Heparin: A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Bacterial Proteins: Proteins found in any species of bacterium.Organic Anion Transporters: Proteins involved in the transport of organic anions. They play an important role in the elimination of a variety of endogenous substances, xenobiotics and their metabolites from the body.Aminobutyrates: Derivatives of BUTYRIC ACID that contain one or more amino groups attached to the aliphatic structure. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the aminobutryrate structure.Thermodynamics: 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)TritiumDNA Primers: 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.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Oligopeptides: Peptides composed of between two and twelve amino acids.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Aptamers, Nucleotide: Nucleotide sequences, generated by iterative rounds of SELEX APTAMER TECHNIQUE, that bind to a target molecule specifically and with high affinity.Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.Vesicular Inhibitory Amino Acid Transport Proteins: A family of vesicular neurotransmitter transporter proteins that sequester the inhibitory neurotransmitters GLYCINE; GAMMA-AMINOBUTYRIC ACID; and possibly GAMMA-HYDROXYBUTYRATE into SECRETORY VESICLES.Circular Dichroism: A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Pregnanolone: A pregnane found in the urine of pregnant women and sows. It has anesthetic, hypnotic, and sedative properties.Receptors, Drug: 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.Oocytes: Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).RNA, Messenger: 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.Cerebral Cortex: The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.Isonicotinic Acids: Heterocyclic acids that are derivatives of 4-pyridinecarboxylic acid (isonicotinic acid).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.Magnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.SepharosePhosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Autoradiography: The making of a radiograph of an object or tissue by recording on a photographic plate the radiation emitted by radioactive material within the object. (Dorland, 27th ed)COS Cells: 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).)Receptors, IgE: Specific molecular sites on the surface of B- and T-lymphocytes which combine with IgEs. Two subclasses exist: low affinity receptors (Fc epsilon RII) and high affinity receptors (Fc epsilon RI).Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Chlorides: Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.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)Neurotransmitter Agents: Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.Receptors, Neurotransmitter: Cell surface receptors that bind signalling molecules released by neurons and convert these signals into intracellular changes influencing the behavior of cells. Neurotransmitter is used here in its most general sense, including not only messengers that act to regulate ion channels, but also those which act on second messenger systems and those which may act at a distance from their release sites. Included are receptors for neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not located at synapses.Models, Biological: 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.Zinc: A metallic element of atomic number 30 and atomic weight 65.38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with ANEMIA, short stature, HYPOGONADISM, impaired WOUND HEALING, and geophagia. It is known by the symbol Zn.Flumazenil: 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.Bicyclo Compounds, Heterocyclic: 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)GABAergic Neurons: Neurons whose primary neurotransmitter is GAMMA-AMINOBUTYRIC ACID.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Tissue Distribution: 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.Temperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Sodium Oxybate: The sodium salt of 4-hydroxybutyric acid. It is used for both induction and maintenance of ANESTHESIA.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.Tumor Cells, Cultured: 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.Neurotransmitter Uptake Inhibitors: Drugs that inhibit the transport of neurotransmitters into axon terminals or into storage vesicles within terminals. For many transmitters, uptake determines the time course of transmitter action so inhibiting uptake prolongs the activity of the transmitter. Blocking uptake may also deplete available transmitter stores. Many clinically important drugs are uptake inhibitors although the indirect reactions of the brain rather than the acute block of uptake itself is often responsible for the therapeutic effects.Interneurons: Most generally any NEURONS which are not motor or sensory. Interneurons may also refer to neurons whose AXONS remain within a particular brain region in contrast to projection neurons, which have axons projecting to other brain regions.Solubility: The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Magnetic 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).SELEX Aptamer Technique: A method of generating a large library of randomized nucleotides and selecting NUCLEOTIDE APTAMERS by iterative rounds of in vitro selection. A modified procedure substitutes AMINO ACIDS in place of NUCLEOTIDES to make PEPTIDE APTAMERS.Strychnine: An alkaloid found in the seeds of STRYCHNOS NUX-VOMICA. It is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of nonketotic hyperglycinemia and sleep apnea, and as a rat poison.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Sodium: A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.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.Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Membranes: Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.Lectins: Proteins that share the common characteristic of binding to carbohydrates. Some ANTIBODIES and carbohydrate-metabolizing proteins (ENZYMES) also bind to carbohydrates, however they are not considered lectins. PLANT LECTINS are carbohydrate-binding proteins that have been primarily identified by their hemagglutinating activity (HEMAGGLUTININS). However, a variety of lectins occur in animal species where they serve diverse array of functions through specific carbohydrate recognition.Protein Engineering: Procedures by which protein structure and function are changed or created in vitro by altering existing or synthesizing new structural genes that direct the synthesis of proteins with sought-after properties. Such procedures may include the design of MOLECULAR MODELS of proteins using COMPUTER GRAPHICS or other molecular modeling techniques; site-specific mutagenesis (MUTAGENESIS, SITE-SPECIFIC) of existing genes; and DIRECTED MOLECULAR EVOLUTION techniques to create new genes.Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.Receptors, Glycine: Cell surface receptors that bind GLYCINE with high affinity and trigger intracellular changes which influence the behavior of cells. Glycine receptors in the CENTRAL NERVOUS SYSTEM have an intrinsic chloride channel and are usually inhibitory.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.Brain Chemistry: Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.Mice, Inbred C57BLFluorescent Dyes: Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.Cerebellum: The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included.Nerve Tissue ProteinsLiver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Cricetulus: 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.Molecular Conformation: The characteristic three-dimensional shape of a molecule.Animals, Newborn: Refers to animals in the period of time just after birth.Convulsants: Substances that act in the brain stem or spinal cord to produce tonic or clonic convulsions, often by removing normal inhibitory tone. They were formerly used to stimulate respiration or as antidotes to barbiturate overdose. They are now most commonly used as experimental tools.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Epitopes: Sites on an antigen that interact with specific antibodies.Swine: 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).Carbolines: 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.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.Cyclic AMP: 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.Biotin: A water-soluble, enzyme co-factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.Xenopus: An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.Crotonates: Derivatives of BUTYRIC ACID that include a double bond between carbon 2 and 3 of the aliphatic structure. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the aminobutryrate structure.Receptors, Serotonin: 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.Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.Proteins: 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.Binding Sites, Antibody: Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.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.Oligodeoxyribonucleotides: A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.Azides: Organic or inorganic compounds that contain the -N3 group.Receptors, Opioid: 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.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Chromatography, Ion Exchange: Separation technique in which the stationary phase consists of ion exchange resins. The resins contain loosely held small ions that easily exchange places with other small ions of like charge present in solutions washed over the resins.GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.Cations, Divalent: Positively charged atoms, radicals or groups of atoms with a valence of plus 2, which travel to the cathode or negative pole during electrolysis.
"α4βδ GABA(A) receptors are high-affinity targets for γ-hydroxybutyric acid (GHB)". Proc. Natl. Acad. Sci. U.S.A. 109 (33): ... It shares no sequence homology with GABAB, and administration of mixed GHB/GABAB receptor agonists along with a selective GABAB ... 2008). "Novel High-Affinity and Selective Biaromatic 4-Substituted gamma-Hydroxybutyric Acid (GHB) Analogues as GHB Ligands: ... The function of the GHB receptor appears to be quite different from that of the GABAB receptor. ...
... the benzodiazepine locks the GABAA receptor into a conformation where the neurotransmitter GABA has much higher affinity for ... "Structural Determinants for High-Affinity Zolpidem Binding to GABA-A receptors". Mol. Pharmacol. 71 (1): 38-46. doi:10.1124/mol ... GABA receptors A review of GABA and the receptors to which it binds. Tocris Cookson LTD. Enz R, Cutting GR (1998). "Molecular ... The ligand GABA is the endogenous compound that causes this receptor to open; once bound to GABA, the protein receptor changes ...
... "α4βδ GABA(A) receptors are high-affinity targets for γ-hydroxybutyric acid (GHB)". Proc. Natl. Acad. Sci. U.S.A. 109 (33): ... "Tonically activated GABAA receptors in hippocampal neurons are high-affinity, low-conductance sensors for extracellular GABA". ... Gabazine binds to the GABA recognition site of the receptor-channel complex and acts as an allosteric inhibitor of channel ... The net effect is to reduce GABA-mediated synaptic inhibition by inhibiting chloride flux across the cell membrane, and thus ...
At high mossy firing frequency (10 Hz) there is no effect of GABA acting on presynaptic GABA-B receptors on evoked EPSCs. ... These high-affinity receptors are located both synaptically and extrasynaptically on the granule cell. The synaptic receptors ... Additionally the GABA acts on GABA-B receptors which are located presynaptically on the mossy fibre terminal. These inhibit the ... However, at low (1 Hz) firing the GABA does have an effect on the EPSCs mediated via these presynaptic GABA-B receptors. Eccles ...
RS-127,445:[34] high affinity; subtype selective (1000x), selective over at least eight other 5-HTR types; orally bioavailable. ... Metadoxine: a 5ht2b antagonist and GABA-activity modulator [35]. *SDZ SER-082: a mixed 5-HT2B/C antagonist ... high affinity, orally bioavailable 5-HT2B receptor antagonist". British Journal of Pharmacology. 127 (5): 1075-82. doi:10.1038/ ... LSD - About equal affinity for human cloned 5-HT2B and 5-HT2A receptors.[28] ...
... high-affinity, steroid modulator of the gamma-aminobutyric acid(A) receptor". The Journal of Pharmacology and Experimental ... Kaminski RM, Livingood MR, Rogawski MA (July 2004). "Allopregnanolone analogs that positively modulate GABA receptors protect ... additional mechanism that provides stabilizing effects that potentially differentiates it from other drugs that increase GABA ...
... has been found to potent (65 times higher affinity than diazepine) GABA-A benzodiapine receptor positive ...
April 2006). "Indiplon is a high-affinity positive allosteric modulator with selectivity for α1 subunit-containing GABA-A ... Zaleplon selectively binds with high efficacy to the benzodiazepine site (ω1) on the α1-containing GABA-A receptors which help ... with lower affinity for the α2 and α3 subsites. It selectively enhances the action of GABA similar to, but more selectively ... but the fast-acting nature and short half-life of the chemical mean high doses set on much more quickly and last for short ...
Relative to other benzodiazepines, lorazepam is thought to have high affinity for GABA receptors, which may also explain its ... A similar lorazepam dose given intravenously will result in an earlier and higher peak serum level, with a higher relative ... high protein binding and anoxidative metabolism to a pharmacologically inactive glucuronide form) and by its high relative ... Because of its high potency, the smallest lorazepam tablet strength of 0.5 mg is also a significant dose reduction (in the UK, ...
... is a selective antagonist of the serotonin receptor subtype 5-HT2B and displays high affinity to the gamma- ... aminobutyric acid (GABA) transporter. In vitro enzymatic assay revealed that metadoxine reduced the activity of the GABA ... and a high sensitivity to being touched. Autism spectrum disorder is seen in approximately 30% of males and 20% of females with ... norepinephrine and GABA: see vitamin B6 functions. L-PGA is present in the diet and is produced endogenously by enzymatic ...
... is a high-affinity positive modulator of GABAA receptors. It selectively binds to α1 subunits of this pentameric ion ... Opposed to diazepam, zolpidem is able to bind to binary αβ GABA receptors, where it was shown to bind to the α1-α1 subunit ... Petroski RE, Pomeroy JE, Das R, Bowman H, Yang W, Chen AP, Foster AC (April 2006). "Indiplon is a high-affinity positive ... Zolpidem has about 10-fold lower affinity for the α2- and α3- subunits than for α1, and no appreciable affinity for α5 subunit- ...
TSPO binds with high affinity to the lipid cholesterol, and pharmacological ligands of TSPO facilitate cholesterol transport ... Bormann J, Ferrero P, Guidotti A, Costa E (1985). "Neuropeptide modulation of GABA receptor C1- channels". Regulatory Peptides ... binds to both TSPO receptor and dihydropyridine-sensitive calcium channels with high affinity. Diazepam binding inhibitor (DBI ... "The polypeptide diazepam-binding inhibitor and a higher affinity mitochondrial peripheral-type benzodiazepine receptor sustain ...
... conductance is not higher in the presence of benzodiazepine and GABA than the conductance with the presence of only high GABA ... Benzodiazepines enhance the receptor affinity for GABA by decreasing the decay of spontaneous miniature inhibitory postsynaptic ... Unlike GABAA receptor agonists, GABAA PAMs do not bind at the same active site as the γ-Aminobutyric acid (GABA) ... GABAA receptors located at synapses are activated when they are exposed to high concentration of GABA. ...
While it is some five times less potent than LY-341,495 at mGluR3, it has 38x higher affinity for mGluR3 over mGluR2, making it ... Glutamate and gaba receptors and transporters: structure, function and pharmacology. pp 171-173. Taylor & Francis, 2002. ISBN 0 ... glycines as High-Affinity Group II Metabotropic Glutamate Receptor Ligands". Bioorganic & Medicinal Chemistry. 11: 197-205. doi ...
... is less selective to the α1 site and has higher affinity to the α2 site than zaleplon. Zopiclone is therefore very ... De, Deyn, Pp; Macdonald, Rl (September 1988). "Effects of non-sedative anxiolytic drugs on responses to GABA and on diazepam- ... April 2006). "Indiplon is a high-affinity positive allosteric modulator with selectivity for alpha1 subunit-containing GABAA ... A high-fat meal preceding zopiclone administration does not change absorption (as measured by AUC), but reduces peak plasma ...
It is weakly active at the 5-HT2, and α2 receptors and is said to have virtually no affinity for the 5-HT1, GABA, mAChRs, α1, ... Ropinirole acts as a D2, D3, and D4 dopamine receptor agonist with highest affinity for D2. ... and at doses higher than clinical, is also metabolized by CYP3A4. At doses greater than 24 mg, CYP2D6 may be inhibited, ...
... is a melatonin receptor agonist with both high affinity for melatonin MT1 and MT2 receptors and selectivity over the ... Ramelteon has no appreciable affinity for the GABA receptor complex or for receptors that bind neuropeptides, cytokines, ... M-II has weak affinity for the serotonin 5-HT2B receptor, but no appreciable affinity for other receptors or enzymes. Similar ... Although the potency of M-II at MT1 and MT2 receptors is lower than the parent drug, M-II circulates at higher concentrations ...
Gesemann M, Brancaccio A, Schumacher B, Ruegg MA (Jan 1998). "Agrin is a high-affinity binding protein of dystroglycan in non- ... "Gephyrin clusters are absent from small diameter primary afferent terminals despite the presence of GABA(A) receptors". The ...
"Structural Determinants for High-Affinity Zolpidem Binding to GABA-A receptors". Mol. Pharmacol. 71 (1): 38-46. PMC 2583146. ... GABAA receptor (GABAAR) je jonotropni receptor i ligandom kontrolisani jonski kanal. Njegov endogeni ligand je γ-aminobuterna ... Aktivno mesto GABAA receptora je mesto vezivanja GABA i nekoliko lekova kao što su muscimol, gaboksadol, i bikuculin. Ovaj ... MeSH Receptors,+GABA-A. *Olsen RW, DeLorey TM (1999). "Chapter 16: GABA and Glycine". u: Siegel GJ, Agranoff BW, Fisher SK, ...
... is a high affinity and selective 5-HT6 receptor full agonist. It induces robust increases in extracellular GABA ...
... whereas those with higher affinity for GABAA receptors containing α2 and/or α3 subunits have good anti-anxiety activity. The ... the benzodiazepine ligand locks the benzodiazepine receptor into a conformation in which it has a greater affinity for the GABA ... Most reports of disinhibition involve high doses of high-potency benzodiazepines. Paradoxical effects may also appear after ... GABA controls the excitability of neurons by binding to the GABAA receptor. The GABAA receptor is a protein complex located in ...
It has higher affinity for α2 containing receptors, where it has positive modulatory activity. In a double-blind placebo- ... Clobazam is a GABA-A receptor agonist action and may affect sodium channels and voltage-sensitive calcium channels. Like other ... The higher the dose and the longer the drug is taken for, the greater the risk of experiencing unpleasant withdrawal symptoms. ... GABA Receptor Agonists". Drugs and Diseases. Medccape. Retrieved 10 July 2005. Ralvenius WT, Acuña MA, Benke D, Matthey A, ...
... which is thought to be due to its high affinity for GABA receptors and to its low lipid solubility, which causes it to remain ... Rubin, Diana; Stephan, Ruegg; Stephan, Marsch; Christian, Schindler; Leticia, Grize; Raoul, Sutter (August 24, 2011). "High ...
... "a4ßd GABA A receptors are high-affinity targets for ¿-hydroxybutyric acid (GHB)" National Academy of Sciences. Proceedings, vol ... hydroxybutyric acid analogues for radiolabeling and photolinking of high-affinity ¿-hydroxybutyric acid binding sites" Journal ... hydroxybutyric acid analogues for radiolabeling and Photolinking of high-affinity {gamma}-hydroxybutyric acid binding sites" ... Madsen, K, Marner, L, Haahr, M, Gillings, N & Knudsen, GM 2011, "Mass dose effects and in vivo affinity in brain PET receptor ...
The GABA neurotransmitter mediates the fast synaptic inhibition in the central nervous system. When GABA is released from its ... At higher doses, ethanol also inhibits the functioning of most ligand- and voltage-gated ion channels. It is not known whether ... ethanol selectively affects these channels via direct low affinity binding or via nonspecific disruption of plasma membranes ... Another receptor for GABA, known as GABAB, can be enhanced by a molecule called baclofen. This molecule acts as an agonist, ...
2008). „Novel High-Affinity and Selective Biaromatic 4-Substituted gamma-Hydroxybutyric Acid (GHB) Analogues as GHB Ligands: ... Funkcija GHB receptora se znatno razlikuje od funkcije GABAB receptora. GHBR nema homolognu sekvencu sa GABAB receptorom, i ... Administracija nespecifičnih GHBR/GABAB agonista zajedno sa selektivnim GABAB antagonistom, ne proizvodi sedativni efekat, ... koja prvenstveno deluju na GABAB receptore, ali takođe pokazuju niz efekata za koje je nađeno da nisu posledica GABAB ...
Four transporters mediate GABA uptake in the brain, GAT1-3 and BGT1. They terminates the action of GABA by high affinity sodium ... GABA Loaded synaptic. vesicle. RIMS1 H+. DAB GABA GABA RAB3A HSPA8 SUCCA. SLC6A GABA. transporters. GABA. GAD1 GABA. b-Ala GAD2 ... GABA VAMP2 GABA STXBP1-1 RAB3A. VAMP2 STX1A RIMS1. STXBP1-1. SNARE complex. GAD1 GAD1 CO2. H2O. SLC6A12. L-Glu. NAD+. GABA. ... GABA. Arrow. R-HSA-888592 (Reactome) GABA. R-HSA-444007 (Reactome) GABA. R-HSA-888592 (Reactome) GABA. R-HSA-916855 (Reactome) ...
α4βδ GABA receptors are high-affinity targets for γ-hydroxybutyric acid (GHB). Research output: Contribution to journal › ... γ-Hydroxybutyric acid (GHB) binding to brain-specific high-affinity sites is well-established and proposed to explain both ... To identify molecular targets for specific GHB high-affinity binding, we undertook photolinking studies combined with proteomic ... Keywords: gamma-hydroxybutyric acid receptor, gamma-hydroxybutyric acid high-affinity binding sites, alpha4-subunit knockout, ...
GDPs are generated by the interplay between glutamate and GABA, which... ... a high-affinity GABA plasma membrane transporter. GABA. γ-Amino-butyric acid ... Owens DF, Kriegstein AR (2002) Is there more to GABA than synaptic inhibition? Nature Rev Neurosci 3:715-727CrossRefGoogle ... Rivera C, Voipio J, Payne JA, Ruusuvuori E, Lahtinen H, Lamsa K, et al (1999) The K+/Cl- co-transporter KCC2 renders GABA ...
Triazoloquinazolinediones as novel high affinity ligands for the benzodiazepine site of GABA(A) receptors. Research output: ... Keywords: 2-aryl-2,6-dihydro[1,2,4]triazolo-[4,3-c]quinazoline-3,5-diones; benzodiazepine binding site; GABA(A) receptors; GABA ... and identified as high-affinity ligands of the binding site. For several compounds, K(i) values of around 0.20nM were ... Based on a pharmacophore model of the benzodiazepine-binding site of GABA(A) receptors, a series of 2-aryl-2,6-dihydro[1,2,4] ...
Although GABA-A receptor-mediated inhibition of cerebellar Purkinje cells by molecular layer interneurons (MLIs) has been ... Although GABA-A receptor-mediated inhibition of cerebellar Purkinje cells by molecular layer interneurons (MLIs) has been ... we permanently disrupted inhibitory fast synaptic transmission at the synapse by genetically removing the postsynaptic GABA-A ... we permanently disrupted inhibitory fast synaptic transmission at the synapse by genetically removing the postsynaptic GABA-A ...
Functional characterization of native, high-affinity GABAA receptors in human pancreatic beta cells (2018). Sergiy V. Korol#, ... The anti-inflammatory effect of GABA may be vital in the pancreatic islets since as long as GABA is present, toxic white blood ... However, there has been no strong link between GABA and type 2 diabetes until recently when it was shown that GABA is important ... They also showed that these ion channels became more sensitive to GABA in type 2 diabetes and that GABA helps regulate insulin ...
Tonic GABA currents mediated by high-affinity extrasynaptic GABAA receptors, are increasingly. Posted on February 7, 2019. by ... Tonic GABA currents mediated by high-affinity extrasynaptic GABAA receptors, are increasingly named essential regulators of ... GABA-activated currents (= 4C13; mean SEM). The peak response to each focus of GABA was assessed with regards to the keeping ... For HEK293 cells, GABA was used alone, or in conjunction with additional drugs utilizing a Y-tube software program (Mortensen ...
Chemotactic responses to BDNF are mediated via TrkB, its high-affinity receptor (Meakin et al., 1992; Behar et al., 1997). The ... Dilutions of GABA between these ranges did not evoke significant (,50 cells/mm2) migration, and higher GABA levels failed to ... At 10 mm[K+]o, motility to GABA is inhibited 50%. At 20 mm[K+]o, migration to GABA is blocked completely. B, Femtomolar GABA- ... Migration to GABA or BDNF was attenuated in the presence of modest elevations in [K+]o (≥7.5 mm). Higher [K+]o levels inhibited ...
The high homology between the cloned skate GABA transporter and the GAT-3 equivalents of other species, coupled with the ... Application of GABA induced a dose-dependent inward current, with 8 muM GABA producing a half-maximal response. The current ... The clone codes for a 622 amino acid protein whose sequence has highest similarity to the GABA/beta-alanine transporter of the ... Termination of GABA signals within the retina occurs through high-affinity reuptake of the released neurotransmitter by GABA ...
2012) α4βδ GABAA receptors are high-affinity targets for γ-hydroxybutyric acid (GHB) Proc Natl Acad Sci USA 109:13404-13409. ... Because of their higher affinity for GABA, extrasynaptic receptors are continuously activated by the small amounts of ... Synaptic GABAA receptors mediate fast phasic inhibition, have a lower affinity for GABA than the extrasynaptic sites, and are ... GABA (3). High- and low-affinity [3H]GHB binding sites are present in rat and human brain (4, 5). Because [3H]GHB binding is ...
OR [44]. In addition, a minor morphine metabolite, morphine-6-glucuronide, showed higher affinity to OR and lower affinity to ... OR surface expression will thus regulate GABA transporter activity. Since reduced GABA reuptake will lead to elevated GABA ... with SGABA representing solution with GABA and solution with additional GAT1-specific inhibitor tiagabine or NNC711. To ... OR led to decreased rate of GAT1-mediated GABA uptake (Figure 2); the dependency was arbitrarily fitted by with half-maximum ...
... it does not bind to GABAA or GABAB receptors, and it does not appear to influence degradation or uptake of GABA. High affinity ... GABA Analog. Pharmacology. Gabapentin is structurally related to GABA. However, ... GA ba pen tin). Dosage Forms. Excipient information presented when available (limited, particularly for generics); consult ... Similarly, a high heterogeneity meta-analysis that included only a limited number of randomized, controlled trials support the ...
Molecular tools for GABAA receptors: High affinity ligands for β1-containing subtypes *Xenia Simeone ... Rights & permissionsfor article Molecular tools for GABA,sub,A,/sub, receptors: High affinity ligands for β1-containing ...
Tonic GABA exerts also a chemotropic action on cell migration. Later on, when synapses are formed, GABA spilled out from ... Tonic GABA exerts also a chemotropic action on cell migration. Later on, when synapses are formed, GABA spilled out from ... GABA exerts its action via synaptic and extrasynaptic GABAA receptors mediating phasic and tonic inhibition, respectively. Here ... GABA exerts its action via synaptic and extrasynaptic GABAA receptors mediating phasic and tonic inhibition, respectively. Here ...
However, γ-CD failed to decrease the basal frequency of sEPSCs in the presence of a non-competitive GABA(A) receptor antagonist ... The AlloP-induced increase in sEPSC frequency was completely blocked by a non-competitive GABA(A) receptor blocker, ... CONCLUSIONS AND IMPLICATIONS The modulation of presynaptic GABA(A) receptors by endogenous neurosteroids might affect the ... tetrodotoxin or Cd(2+) , suggesting that AlloP acts on presynaptic GABA(A) receptors to depolarize presynaptic nerve terminals ...
Vigabatrin is a structural derivative of GABA. Its mechanism of action is unknown. Vigabatrin binds with high affinity to the ... It is structurally related to GABA but does not affect GABA directly, although it is thought to modulate the calcium channel. ... This drug enhances GABA activity by inhibiting uptake in neurons and astrocytes. Tiagabine can be used as an add-on therapy for ... However, felbamate has a high rate of life-threatening side effects, so the benefits and risks of the drug need to be carefully ...
A) Comparison of 14C-GABA uptake into X. laevis oocytes expressing TaALMT1 and AtGAT1 high-affinity GABA transporter at pH 4.5 ... Influx mode will tend to reduce [GABA]o and increase [GABA]i (orange = high [GABA]; purple = low [GABA]). Efflux modes (center ... or GABA as the sole nitrogen source; it was used to characterize high affinity GABA transport (Meyer et al., 2006). The efflux ... GABA]i (Figure 1). We also confirmed that line ET8 had higher [GABA]i than ES8 in pH 4.5 and that ES8 [GABA]i did not respond ...
Sodium Dependent, High Affinity Choline Transport Expressed in Oocytes. Comparison of the Effects of Vesamicol and of Cetiedil ... GABA Uptake Inhibitors: Kinetics and Molecular Pharmacology. Coexistance of More than One Neurotransitter Uptake System on the ... Transmitter Interactions in Striatum may occur via Effects on High Affinity Transporters. A Comparison of the Effect of ... Identification and Regulation of High-Affinity-Choline Transporter. Ketanserin as a Ligand of the Vesicular Monoamine ...
Rabbit polyclonal GABA Transporter 1 / GAT 1 antibody validated for WB, IHC and tested in Mouse and Rat. Referenced in 1 ... Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals. ... Anti-GABA Transporter 1 / GAT 1 antibody. See all GABA Transporter 1 / GAT 1 primary antibodies. ... Sodium- and chloride-dependent GABA transporter 1 antibody. *Solute carrier family 6 (neurotransmitter transporter GABA) member ...
Rabbit polyclonal GABA Transporter 3 / GAT 3 antibody. Validated in WB, IHC and tested in Human. Immunogen corresponding to ... Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals. ... Anti-GABA Transporter 3 / GAT 3 antibody. See all GABA Transporter 3 / GAT 3 primary antibodies. ... All lanes : Anti-GABA Transporter 3 / GAT 3 antibody (ab122430) at 1/250 dilution. Lane 1 : RT-4 cell lysate. Lane 2 : U-251 MG ...
... the benzodiazepine locks the GABAA receptor into a conformation where the neurotransmitter GABA has much higher affinity for ... "Structural Determinants for High-Affinity Zolpidem Binding to GABA-A receptors". Mol. Pharmacol. 71 (1): 38-46. doi:10.1124/mol ... GABA receptors A review of GABA and the receptors to which it binds. Tocris Cookson LTD. Enz R, Cutting GR (1998). "Molecular ... The ligand GABA is the endogenous compound that causes this receptor to open; once bound to GABA, the protein receptor changes ...
1992) Multiple types of high-threshold calcium channels in rabbit sensory neurons: high-affinity block of neuronal L-type by ... The two primary GABA receptors are the ionotropic GABAA receptor that opens Cl− channels and the G-protein-coupled GABAB ... Ca2+ rises elicited by 10 μm GABA sometimes were greater than the response to higher concentrations of NMDA (100 μm). F, This ... The GABAAantagonist bicuculline (20 μm) blocked the Ca2+ elevating actions of GABA (Fig.4 A-C). Muscimol (10 μm), a specific ...
"α4βδ GABA(A) receptors are high-affinity targets for γ-hydroxybutyric acid (GHB)". Proc. Natl. Acad. Sci. U.S.A. 109 (33): ... It shares no sequence homology with GABAB, and administration of mixed GHB/GABAB receptor agonists along with a selective GABAB ... 2008). "Novel High-Affinity and Selective Biaromatic 4-Substituted gamma-Hydroxybutyric Acid (GHB) Analogues as GHB Ligands: ... The function of the GHB receptor appears to be quite different from that of the GABAB receptor. ...
While benzodiazepines have a high affinity for several subunits, Z-drugs mostly bind to the α-1-subunit [13]. ... The GABA-A-receptor complex consists of several heterogenic subunits; the different subunits and their combination create ... We can only speculate as to whether genetic variation in the function of the GABA receptor subunit genes had a role in ... Flumazenil acts as an antagonist on the GABA-A receptor and is primarily used as antidote in benzodiazepine intoxication and ...
The drug binds with high affinity to the alpha2-delta site (a calcium channel subunit). In vitro, it reduces the calcium- ... Pregabalin is a structural derivative of gamma-aminobutyric acid (GABA). Its mechanism of action is unknown. ... Doses higher than 75 mg do not increase the therapeutic effects. Administer high doses with caution, and closely observe the ... Gabapentin, a membrane stabilizer, is a structural analogue of the inhibitory neurotransmitter GABA, although, paradoxically, ...
  • GAD65 and VGAT are functionally linked at the synaptic vesicle membrane and GABA synthesized by GAD65 is preferentially loaded into the synaptic vesicle over GABA synthesized in cytoplasm by GAD67.The GABA loaded synaptic vesicles are docked at the plasma membrane with the help of the SNARE complexes and primed by interplay between various proteins including Munc18, complexin etc. (wikipathways.org)
  • Release of GABA loaded synaptic vesicle is initiated by the arrival of action potential at the presynaptic bouton and opening of N or P/Q voltage gated Ca2+ channels. (wikipathways.org)
  • A novel mechanism for GABA synthesis and packaging into synaptic vesicles. (wikipathways.org)
  • GABA synthesized by GAD65 is used for neurotransmission whereas GABA synthesized by GAD67 is used for processes other than neurotransmission such as synaptogenesis and protection against neuronal injury. (wikipathways.org)
  • Disruption of GABA neurotransmission leads to many neurological diseases including epilepsy and a general anxiety disorder. (wikipathways.org)
  • GABA is synthesized by two distinct enzymes GAD67 and GAD65 that differ in their cellular localization, functional properties and co-factor requirements. (wikipathways.org)
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