Derivatives of GLUTAMIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure.

Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells. Glutamate receptors include ionotropic receptors (AMPA, kainate, and N-methyl-D-aspartate receptors), which directly control ion channels, and metabotropic receptors which act through second messenger systems. Glutamate receptors are the most common mediators of fast excitatory synaptic transmission in the central nervous system. They have also been implicated in the mechanisms of memory and of many diseases.

A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.

The study of the composition, chemical structures, and chemical reactions of living things.

An enzyme that catalyzes the conversion of L-glutamate and water to 2-oxoglutarate and NH3 in the presence of NAD+. (From Enzyme Nomenclature, 1992) EC 1.4.1.2.

Cell surface proteins that bind glutamate and act through G-proteins to influence second messenger systems. Several types of metabotropic glutamate receptors have been cloned. They differ in pharmacology, distribution, and mechanisms of action.

One of the FLAVORING AGENTS used to impart a meat-like flavor.

A family of POTASSIUM and SODIUM-dependent acidic amino acid transporters that demonstrate a high affinity for GLUTAMIC ACID and ASPARTIC ACID. Several variants of this system are found in neuronal tissue.

An enzyme that catalyzes the formation of 2 molecules of glutamate from glutamine plus alpha-ketoglutarate in the presence of NADPH. EC 1.4.1.13.

A family of plasma membrane neurotransmitter transporter proteins that couple the uptake of GLUTAMATE with the import of SODIUM ions and PROTONS and the export of POTASSIUM ions. In the CENTRAL NERVOUS SYSTEM they regulate neurotransmission through synaptic reuptake of the excitatory neurotransmitter glutamate. Outside the central nervous system they function as signal mediators and regulators of glutamate metabolism.

A type I G protein-coupled receptor mostly expressed post-synaptic pyramidal cells of the cortex and CENTRAL NERVOUS SYSTEM.

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.

A family of vesicular neurotransmitter transporter proteins that were originally characterized as sodium dependent inorganic phosphate cotransporters. Vesicular glutamate transport proteins sequester the excitatory neurotransmitter GLUTAMATE from the CYTOPLASM into SECRETORY VESICLES in exchange for lumenal PROTONS.

Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.

A glutamate plasma membrane transporter protein found in ASTROCYTES and in the LIVER.

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.

A vesicular glutamate transporter protein that is predominately expressed in the DIENCEPHALON and lower brainstem regions of the CENTRAL NERVOUS SYSTEM.

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 rate dynamics in chemical or physical systems.

One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.

A class of ionotropic glutamate receptors characterized by their affinity for the agonist AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid).

A vesicular glutamate transporter protein that is predominately expressed in TELENCEPHALON of the BRAIN.

Drugs that bind to and activate excitatory amino acid receptors.

A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.

A glial type glutamate plasma membrane transporter protein found predominately in ASTROCYTES. It is also expressed in HEART and SKELETAL MUSCLE and in the PLACENTA.

A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from GLUTAMIC ACID and AMMONIA. It is the principal carrier of NITROGEN in the body and is an important energy source for many cells.

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.

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.

A neuronal and epithelial type glutamate plasma membrane transporter protein.

A class of ligand-gated ion channel receptors that have specificity for GLUTAMATE. They are distinct from METABOTROPIC GLUTAMATE RECEPTORS which act through a G-protein-coupled mechanism.

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.

(2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose.

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

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.

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

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.

A class of ionotropic glutamate receptors characterized by their affinity for KAINIC ACID.

An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).

An IBOTENIC ACID homolog and glutamate agonist. The compound is the defining agonist for the AMPA subtype of glutamate receptors (RECEPTORS, AMPA). It has been used as a radionuclide imaging agent but is more commonly used as an experimental tool in cell biological studies.

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 chemical processes, enzymatic activities, and pathways of living things and related temporal, dimensional, qualitative, and quantitative concepts.

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.

An amino acid formed by cyclization of leucine. It has cytostatic, immunosuppressive and antineoplastic activities.

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.

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.

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).

Amino acid transporter systems capable of transporting acidic amino acids (AMINO ACIDS, ACIDIC).

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.

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 basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.

A 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.

Depolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during neurotransmission. Excitatory postsynaptic potentials can singly or in summation reach the trigger threshold for ACTION POTENTIALS.

The most common inhibitory neurotransmitter in the central nervous system.

An agonist at two subsets of excitatory amino acid receptors, ionotropic receptors that directly control membrane channels and metabotropic receptors that indirectly mediate calcium mobilization from intracellular stores. The compound is obtained from the seeds and fruit of Quisqualis chinensis.

A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury.

Proteins prepared by recombinant DNA technology.

An enzyme that catalyzes the conversion of ATP, L-glutamate, and NH3 to ADP, orthophosphate, and L-glutamine. It also acts more slowly on 4-methylene-L-glutamate. (From Enzyme Nomenclature, 1992) EC 6.3.1.2.

A potent excitatory amino acid antagonist with a preference for non-NMDA iontropic receptors. It is used primarily as a research tool.

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

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.

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.

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

A family of compounds containing an oxo group with the general structure of 1,5-pentanedioic acid. (From Lehninger, Principles of Biochemistry, 1982, p442)

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)

Established cell cultures that have the potential to propagate indefinitely.

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

A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.

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

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

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.

Quinoxalines are heterocyclic organic compounds consisting of a benzene fused to a pyrazine ring, which have been studied for their potential antibacterial, antifungal, and anticancer properties.

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.

The D-enantiomer is a potent and specific antagonist of NMDA glutamate receptors (RECEPTORS, N-METHYL-D-ASPARTATE). The L form is inactive at NMDA receptors but may affect the AP4 (2-amino-4-phosphonobutyrate; APB) excitatory amino acid receptors.

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.

A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane.

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.

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.

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

A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as AMMONIUM HYDROXIDE.

A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.

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)

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.

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.

Proteins found in any species of bacterium.

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.

Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.

Glutaminase is an enzyme that catalyzes the conversion of glutamine to glutamate and ammonia, playing a crucial role in nitrogen metabolism and amino acid homeostasis within various tissues and cells, including the brain, kidney, and immune cells.

Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear.

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.

'Amino Acid Transport System y+', also known as System Y+, is a sodium-independent cationic amino acid transporter that mediates the uptake of primarily basic amino acids, such as arginine and lysine, into cells through a facilitated diffusion process.

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.

A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).

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.

A metallocarboxypeptidase that is predominantly expressed as a membrane-bound enzyme. It catalyzes the hydrolysis of an unsubstituted, C-terminal glutamyl residue, typically from PTEROYLPOLYGLUTAMIC ACIDS. It was formerly classified as EC 3.4.19.8.

A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. (Dorland, 28th ed) EC 2.6.1.

A broad-spectrum excitatory amino acid antagonist used as a research tool.

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

Drugs used for their actions on any aspect of excitatory amino acid neurotransmitter systems. Included are drugs that act on excitatory amino acid receptors, affect the life cycle of excitatory amino acid transmitters, or affect the survival of neurons using excitatory amino acids.

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.

Dicarboxylic acids are organic compounds containing two carboxyl (-COOH) groups in their structure, making them capable of forming salts and esters by losing two hydrogen ions.

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

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.

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).

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.

Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.

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.

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).

The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.

Refers to animals in the period of time just after birth.

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

Resorcinols are aromatic organic compounds containing two hydroxyl groups attached to a benzene ring, known for their antiseptic and antibacterial properties, used in various medical and cosmetic applications.

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 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.

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.

A glutamate plasma membrane transporter protein that is primarily expressed in cerebellar PURKINJE CELLS on postsynaptic DENDRITIC SPINES.

Synthesized from endogenous epinephrine and norepinephrine in vivo. It is found in brain, blood, CSF, and urine, where its concentrations are used to measure catecholamine turnover.

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 non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the BLOOD-BRAIN BARRIER and BLOOD-RETINAL BARRIER, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear.

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.

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.

'Nerve tissue proteins' are specialized proteins found within the nervous system's biological tissue, including neurofilaments, neuronal cytoskeletal proteins, and neural cell adhesion molecules, which facilitate structural support, intracellular communication, and synaptic connectivity essential for proper neurological function.

Heterocyclic compounds of a ring with SULFUR and two NITROGEN atoms fused to a BENZENE ring. Members inhibit SODIUM-POTASSIUM-CHLORIDE SYMPORTERS and are used as DIURETICS.

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

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.

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.

A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.

Use of electric potential or currents to elicit biological responses.

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.

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.

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.

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 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)

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.

The sum of the weight of all the atoms in a molecule.

Measurement of the intensity and quality of fluorescence.

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.

A covalently linked dimeric nonessential amino acid formed by the oxidation of CYSTEINE. Two molecules of cysteine are joined together by a disulfide bridge to form cystine.

A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.

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.

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

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.

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.

Histochemical localization of immunoreactive substances using labeled antibodies as reagents.

Interstitial space between cells, occupied by INTERSTITIAL FLUID as well as amorphous and fibrous substances. For organisms with a CELL WALL, the extracellular space includes everything outside of the CELL MEMBRANE including the PERIPLASM and the cell wall.

DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.

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

A series of oxidative reactions in the breakdown of acetyl units derived from GLUCOSE; FATTY ACIDS; or AMINO ACIDS by means of tricarboxylic acid intermediates. The end products are CARBON DIOXIDE, water, and energy in the form of phosphate bonds.

A glutamate plasma membrane transporter protein that is primarily expressed in the RETINA.

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.

Compounds with three aromatic rings in linear arrangement with an OXYGEN in the center ring.

The capacity of the NERVOUS SYSTEM to change its reactivity as the result of successive activations.

Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion.

Projection neurons in the CEREBRAL CORTEX and the HIPPOCAMPUS. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region.

Enzymes of the transferase class that catalyze the conversion of L-aspartate and 2-ketoglutarate to oxaloacetate and L-glutamate. EC 2.6.1.1.

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 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)

A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed)

Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.

A neurotoxic isoxazole (similar to KAINIC ACID and MUSCIMOL) found in AMANITA mushrooms. It causes motor depression, ataxia, and changes in mood, perceptions and feelings, and is a potent excitatory amino acid agonist.

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.

Extensions of the nerve cell body. They are short and branched and receive stimuli from other NEURONS.

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.

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.

Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.

The process of cleaving a chemical compound by the addition of a molecule of water.

Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5'-phosphate (NMN) coupled by pyrophosphate linkage to the 5'-phosphate adenosine 2',5'-bisphosphate. It serves as an electron carrier in a number of reactions, being alternately oxidized (NADP+) and reduced (NADPH). (Dorland, 27th ed)

Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.

Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)

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.

Stable carbon atoms that have the same atomic number as the element carbon, but differ in atomic weight. C-13 is a stable carbon isotope.

An examination of chemicals in the blood.

Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.

An element with the atomic symbol N, atomic number 7, and atomic weight [14.00643; 14.00728]. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells.

A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.

Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.

The study of the structure, preparation, properties, and reactions of carbon compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)

Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.

The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.

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.

The output neurons of the cerebellar cortex.

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.

Membrane transporters that co-transport two or more dissimilar molecules in the same direction across a membrane. Usually the transport of one ion or molecule is against its electrochemical gradient and is "powered" by the movement of another ion or molecule with its electrochemical gradient.

A FLAVOPROTEIN enzyme for AMMONIA assimilation in BACTERIA, microorganisms and PLANTS. It catalyzes the oxidation of 2 molecules of L-GLUTAMATE to generate L-GLUTAMINE and 2-oxoglutarate in the presence of NAD+.

A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.

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.

Neurotransmitter receptors located on or near presynaptic terminals or varicosities. Presynaptic receptors which bind transmitter molecules released by the terminal itself are termed AUTORECEPTORS.

A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory.

The specialty of ANALYTIC CHEMISTRY applied to assays of physiologically important substances found in blood, urine, tissues, and other biological fluids for the purpose of aiding the physician in making a diagnosis or following therapy.

The function of opposing or restraining the excitation of neurons or their target excitable cells.

A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.

Proteins obtained from ESCHERICHIA COLI.

"Malate" is a term used in biochemistry to refer to a salt or ester of malic acid, a dicarboxylic acid found in many fruits and involved in the citric acid cycle, but it does not have a specific medical definition as such.

Derivatives of BENZOIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxybenzene structure.

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 family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.

Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.

Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.

Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents.