alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid: 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.Receptors, AMPA: A class of ionotropic glutamate receptors characterized by their affinity for the agonist AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid).Benzothiadiazines: 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.Kainic Acid: (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.Receptors, Glutamate: 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.Receptors, Kainic Acid: A class of ionotropic glutamate receptors characterized by their affinity for KAINIC ACID.Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.Excitatory Amino Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors.Receptors, N-Methyl-D-Aspartate: 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.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.6-Cyano-7-nitroquinoxaline-2,3-dione: A potent excitatory amino acid antagonist with a preference for non-NMDA iontropic receptors. It is used primarily as a research tool.QuinoxalinesN-Methylaspartate: An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).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.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.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.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.Quisqualic Acid: 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.Ibotenic Acid: 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.2-Amino-5-phosphonovalerate: 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.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.Excitatory Postsynaptic Potentials: 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.Carbocysteine: A compound formed when iodoacetic acid reacts with sulfhydryl groups in proteins. It has been used as an anti-infective nasal spray with mucolytic and expectorant action.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.Benzodiazepines: A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring.Cycloleucine: An amino acid formed by cyclization of leucine. It has cytostatic, immunosuppressive and antineoplastic activities.Excitatory Amino Acid Agents: 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.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.Receptors, Metabotropic Glutamate: 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.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.Glutamates: 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.Long-Term Potentiation: 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.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.Electric Stimulation: Use of electric potential or currents to elicit biological responses.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.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.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.Dizocilpine Maleate: 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.Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other NEURONS.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.Evoked Potentials: Electrical responses recorded from nerve, muscle, SENSORY RECEPTOR, or area of the CENTRAL NERVOUS SYSTEM following stimulation. They range from less than a microvolt to several microvolts. The evoked potential can be auditory (EVOKED POTENTIALS, AUDITORY), somatosensory (EVOKED POTENTIALS, SOMATOSENSORY), visual (EVOKED POTENTIALS, VISUAL), or motor (EVOKED POTENTIALS, MOTOR), or other modalities that have been reported.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.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.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).Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Dimethyl Adipimidate: Bifunctional cross-linking agent that links covalently free amino groups of proteins or polypeptides, including those in cell membranes. It is used as reagent or fixative in immunohistochemistry and is a proposed antisickling agent.Pyramidal Cells: 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.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.Neuronal Plasticity: The capacity of the NERVOUS SYSTEM to change its reactivity as the result of successive activations.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.Bicuculline: An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.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.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.Kinetics: The rate dynamics in chemical or physical systems.Organ Culture Techniques: A technique for maintenance or growth of animal organs in vitro. It refers to three-dimensional cultures of undisaggregated tissue retaining some or all of the histological features of the tissue in vivo. (Freshney, Culture of Animal Cells, 3d ed, p1)Anticonvulsants: Drugs used to prevent SEIZURES or reduce their severity.Spinal Cord: A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.Animals, Newborn: Refers to animals in the period of time just after birth.Mice, Inbred C57BLProtein Transport: 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.Nerve Tissue ProteinsSeizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."Tetrodotoxin: An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Signal Transduction: 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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Mice, Knockout: 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.Receptors, Adrenergic, alpha: One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.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.Models, Neurological: Theoretical representations that simulate the behavior or activity of the neurological system, processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Hypoxia-Inducible Factor 1, alpha Subunit: Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.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.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.NG-Nitroarginine Methyl Ester: A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.Methyl Parathion: The methyl homolog of parathion. An effective, but highly toxic, organothiophosphate insecticide and cholinesterase inhibitor.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Neurotoxins: 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.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.alpha7 Nicotinic Acetylcholine Receptor: A member of the NICOTINIC ACETYLCHOLINE RECEPTOR subfamily of the LIGAND-GATED ION CHANNEL family. It consists entirely of pentameric a7 subunits expressed in the CNS, autonomic nervous system, vascular system, lymphocytes and spleen.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.Integrin alpha3beta1: Cell surface receptor for LAMININ, epiligrin, FIBRONECTINS, entactin, and COLLAGEN. Integrin alpha3beta1 is the major integrin present in EPITHELIAL CELLS, where it plays a role in the assembly of BASEMENT MEMBRANE as well as in cell migration, and may regulate the functions of other integrins. Two alternatively spliced isoforms of the alpha subunit (INTEGRIN ALPHA3), are differentially expressed in different cell types.Integrin alpha4: An integrin alpha subunit that is unique in that it does not contain an I domain, and its proteolytic cleavage site is near the middle of the extracellular portion of the polypeptide rather than close to the membrane as in other integrin alpha subunits.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.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.Integrin alpha6: An integrin alpha subunit that primarily associates with INTEGRIN BETA1 or INTEGRIN BETA4 to form laminin-binding heterodimers. Integrin alpha6 has two alternatively spliced isoforms: integrin alpha6A and integrin alpha6B, which differ in their cytoplasmic domains and are regulated in a tissue-specific and developmental stage-specific manner.Neuroprotective Agents: 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.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.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.Integrin alpha5beta1: An integrin found in FIBROBLASTS; PLATELETS; MONOCYTES, and LYMPHOCYTES. Integrin alpha5beta1 is the classical receptor for FIBRONECTIN, but it also functions as a receptor for LAMININ and several other EXTRACELLULAR MATRIX PROTEINS.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.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).Methyl Methanesulfonate: An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.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.Amino Acids, Essential: Amino acids that are not synthesized by the human body in amounts sufficient to carry out physiological functions. They are obtained from dietary foodstuffs.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Integrin alpha4beta1: Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR MATRIX adhesion and plays a role in INFLAMMATION, hematopoietic cell homing and immune function, and has been implicated in skeletal MYOGENESIS; NEURAL CREST migration and proliferation, lymphocyte maturation and morphogenesis of the PLACENTA and HEART.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).Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Interleukin-1alpha: An interleukin-1 subtype that occurs as a membrane-bound pro-protein form that is cleaved by proteases to form a secreted mature form. Unlike INTERLEUKIN-1BETA both membrane-bound and secreted forms of interleukin-1alpha are biologically active.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.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.Receptors, Adrenergic, alpha-1: A subclass of alpha-adrenergic receptors that mediate contraction of SMOOTH MUSCLE in a variety of tissues such as ARTERIOLES; VEINS; and the UTERUS. They are usually found on postsynaptic membranes and signal through GQ-G11 G-PROTEINS.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Amygdala: Almond-shaped group of basal nuclei anterior to the INFERIOR HORN OF THE LATERAL VENTRICLE of the TEMPORAL LOBE. The amygdala is part of the limbic system.Integrin alpha2beta1: An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Integrin alpha5: This integrin alpha subunit combines with INTEGRIN BETA1 to form a receptor (INTEGRIN ALPHA5BETA1) that binds FIBRONECTIN and LAMININ. It undergoes posttranslational cleavage into a heavy and a light chain that are connected by disulfide bonds.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.Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.Integrin alpha1beta1: Integrin alpha1beta1 functions as a receptor for LAMININ and COLLAGEN. It is widely expressed during development, but in the adult is the predominant laminin receptor (RECEPTORS, LAMININ) in mature SMOOTH MUSCLE CELLS, where it is important for maintenance of the differentiated phenotype of these cells. Integrin alpha1beta1 is also found in LYMPHOCYTES and microvascular endothelial cells, and may play a role in angiogenesis. In SCHWANN CELLS and neural crest cells, it is involved in cell migration. Integrin alpha1beta1 is also known as VLA-1 and CD49a-CD29.Receptors, Adrenergic, alpha-2: A subclass of alpha-adrenergic receptors found on both presynaptic and postsynaptic membranes where they signal through Gi-Go G-PROTEINS. While postsynaptic alpha-2 receptors play a traditional role in mediating the effects of ADRENERGIC AGONISTS, the subset of alpha-2 receptors found on presynaptic membranes signal the feedback inhibition of NEUROTRANSMITTER release.Amino Acid Transport Systems: Cellular proteins and protein complexes that transport amino acids across biological membranes.Integrin alpha6beta1: A cell surface receptor mediating cell adhesion to the EXTRACELLULAR MATRIX and to other cells via binding to LAMININ. It is involved in cell migration, embryonic development, leukocyte activation and tumor cell invasiveness. Integrin alpha6beta1 is the major laminin receptor on PLATELETS; LEUKOCYTES; and many EPITHELIAL CELLS, and ligand binding may activate a number of signal transduction pathways. Alternative splicing of the cytoplasmic domain of the alpha6 subunit (INTEGRIN ALPHA6) results in the formation of A and B isoforms of the heterodimer, which are expressed in a tissue-specific manner.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.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.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.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.Molecular Weight: The sum of the weight of all the atoms in a molecule.Integrin alpha6beta4: This intrgrin is a key component of HEMIDESMOSOMES and is required for their formation and maintenance in epithelial cells. Integrin alpha6beta4 is also found on thymocytes, fibroblasts, and Schwann cells, where it functions as a laminin receptor (RECEPTORS, LAMININ) and is involved in wound healing, cell migration, and tumor invasiveness.Methyl Chloride: A hydrocarbon used as an industrial solvent. It has been used as an aerosal propellent, as a refrigerant and as a local anesthetic. (From Martindale, The Extra Pharmacopoeia, 31st ed, p1403)Sequence Homology, Nucleic Acid: The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.Integrins: A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.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.Integrin alpha Chains: The alpha subunits of integrin heterodimers (INTEGRINS), which mediate ligand specificity. There are approximately 18 different alpha chains, exhibiting great sequence diversity; several chains are also spliced into alternative isoforms. They possess a long extracellular portion (1200 amino acids) containing a MIDAS (metal ion-dependent adhesion site) motif, and seven 60-amino acid tandem repeats, the last 4 of which form EF HAND MOTIFS. The intracellular portion is short with the exception of INTEGRIN ALPHA4.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Integrin alpha1: An integrin alpha subunit that binds COLLAGEN and LAMININ though its I domain. It combines with INTEGRIN BETA1 to form the heterodimer INTEGRIN ALPHA1BETA1.Gene Expression Regulation: 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.DNA 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.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.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.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.Alpha Rhythm: Brain waves characterized by a relatively high voltage or amplitude and a frequency of 8-13 Hz. They constitute the majority of waves recorded by EEG registering the activity of the parietal and occipital lobes when the individual is awake, but relaxed with the eyes closed.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).

Estradiol increases spine density and NMDA-dependent Ca2+ transients in spines of CA1 pyramidal neurons from hippocampal slices. (1/683)

To investigate the physiological consequences of the increase in spine density induced by estradiol in pyramidal neurons of the hippocampus, we performed simultaneous whole cell recordings and Ca2+ imaging in CA1 neuron spines and dendrites in hippocampal slices. Four- to eight-days in vitro slice cultures were exposed to 17beta-estradiol (EST) for an additional 4- to 8-day period, and spine density was assessed by confocal microscopy of DiI-labeled CA1 pyramidal neurons. Spine density was doubled in both apical and basal dendrites of the CA1 region in EST-treated slices; consistently, a reduction in cell input resistance was observed in EST-treated CA1 neurons. Double immunofluorescence staining of presynaptic (synaptophysin) and postsynaptic (alpha-subunit of CaMKII) proteins showed an increase in synaptic density after EST treatment. The slopes of the input/output curves of both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) postsynaptic currents were steeper in EST-treated CA1 neurons, consistent with the observed increase in synapse density. To characterize NMDA-dependent synaptic currents and dendritic Ca2+ transients during Schaffer collaterals stimulation, neurons were maintained at +40 mV in the presence of nimodipine, picrotoxin, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). No differences in resting spine or dendritic Ca2+ levels were observed between control and EST-treated CA1 neurons. Intracellular Ca2+ transients during afferent stimulation exhibited a faster slope and reached higher levels in spines than in adjacent dendrites. Peak Ca2+ levels were larger in both spines and dendrites of EST-treated CA1 neurons. Ca2+ gradients between spine heads and dendrites during afferent stimulation were also larger in EST-treated neurons. Both spine and dendritic Ca2+ transients during afferent stimulation were reversibly blocked by D, L-2-amino-5-phosphonovaleric acid (D,L-APV). The increase in spine density and the enhanced NMDA-dependent Ca2+ signals in spines and dendrites induced by EST may underlie a threshold reduction for induction of NMDA-dependent synaptic plasticity in the hippocampus.  (+info)

Recurrent mossy fiber pathway in rat dentate gyrus: synaptic currents evoked in presence and absence of seizure-induced growth. (2/683)

A common feature of temporal lobe epilepsy and of animal models of epilepsy is the growth of hippocampal mossy fibers into the dentate molecular layer, where at least some of them innervate granule cells. Because the mossy fibers are axons of granule cells, the recurrent mossy fiber pathway provides monosynaptic excitatory feedback to these neurons that could facilitate seizure discharge. We used the pilocarpine model of temporal lobe epilepsy to study the synaptic responses evoked by activating this pathway. Whole cell patch-clamp recording demonstrated that antidromic stimulation of the mossy fibers evoked an excitatory postsynaptic current (EPSC) in approximately 74% of granule cells from rats that had survived >10 wk after pilocarpine-induced status epilepticus. Recurrent mossy fiber growth was demonstrated with the Timm stain in all instances. In contrast, antidromic stimulation of the mossy fibers evoked an EPSC in only 5% of granule cells studied 4-6 days after status epilepticus, before recurrent mossy fiber growth became detectable. Notably, antidromic mossy fiber stimulation also evoked an EPSC in many granule cells from control rats. Clusters of mossy fiber-like Timm staining normally were present in the inner third of the dentate molecular layer at the level of the hippocampal formation from which slices were prepared, and several considerations suggested that the recorded EPSCs depended mainly on activation of recurrent mossy fibers rather than associational fibers. In both status epilepticus and control groups, the antidromically evoked EPSC was glutamatergic and involved the activation of both AMPA/kainate and N-methyl-D-aspartate (NMDA) receptors. EPSCs recorded in granule cells from rats with recurrent mossy fiber growth differed in three respects from those recorded in control granule cells: they were much more frequently evoked, a number of them were unusually large, and the NMDA component of the response was generally much more prominent. In contrast to the antidromically evoked EPSC, the EPSC evoked by stimulation of the perforant path appeared to be unaffected by a prior episode of status epilepticus. These results support the hypothesis that recurrent mossy fiber growth and synapse formation increases the excitatory drive to dentate granule cells and thus facilitates repetitive synchronous discharge. Activation of NMDA receptors in the recurrent pathway may contribute to seizure propagation under depolarizing conditions. Mossy fiber-granule cell synapses also are present in normal rats, where they may contribute to repetitive granule cell discharge in regions of the dentate gyrus where their numbers are significant.  (+info)

Differences in the properties of ionotropic glutamate synaptic currents in oxytocin and vasopressin neuroendocrine neurons. (3/683)

Oxytocin (OT) and vasopressin (VP) hormone release from neurohypophysial terminals is controlled by the firing pattern of neurosecretory cells located in the hypothalamic supraoptic (SON) and paraventricular nuclei. Although glutamate is a key modulator of the electrical activity of both OT and VP neurons, a differential contribution of AMPA receptors (AMPARs) and NMDA receptors (NMDARs) has been proposed to mediate glutamatergic influences on these neurons. In the present study we examined the distribution and functional properties of synaptic currents mediated by AMPARs and NMDARs in immunoidentified SON neurons. Our results suggest that the properties of AMPA-mediated currents in SON neurons are controlled in a cell type-specific manner. OT neurons displayed AMPA-mediated miniature EPSCs (mEPSCs) with larger amplitude and faster decay kinetics than VP neurons. Furthermore, a peak-scaled nonstationary noise analysis of mEPSCs revealed a larger estimated single-channel conductance of AMPARs expressed in OT neurons. High-frequency summation of AMPA-mediated excitatory postsynaptic potentials was smaller in OT neurons. In both cell types, AMPA-mediated synaptic currents showed inward rectification, which was more pronounced in OT neurons, and displayed Ca2+ permeability. On the other hand, NMDA-mediated mEPSCs of both cell types had similar amplitude and kinetic properties. The cell type-specific expression of functionally different AMPARs can contribute to the adoption of different firing patterns by these neuroendocrine neurons in response to physiological stimuli.  (+info)

Clozapine, but not haloperidol, prevents the functional hyperactivity of N-methyl-D-aspartate receptors in rat cortical neurons induced by subchronic administration of phencyclidine. (4/683)

Repeated exposure of rats to the psychotomimetic drug phencyclidine (PCP) markedly increased the response of prefrontal cortical neurons to the glutamate agonist N-methyl-D-aspartate (NMDA) relative to agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid. Moreover, acute challenge by PCP produced a significantly reduced block of NMDA-induced current. In addition, the subchronic administration of PCP reduced significantly the paired-pulse facilitation, accompanied by a significant increase of excitatory postsynaptic current variance. These results suggest that repeated exposure to PCP increased evoked release of excitatory amino acids. The enhanced release of excitatory amino acids evoked by NMDA could explain, at least partly, a hypersensitive response to NMDA and a reduced blockade of the NMDA responses by a PCP challenge in rats exposed repeatedly to PCP. Pretreatment with the atypical antipsychotic drug clozapine, but not the typical antipsychotic drug haloperidol, attenuates the repeated PCP-induced effect. Our results support the hypothesis that clozapine may facilitate NMDA receptor-mediated neurotransmission to improve schizophrenic-negative symptoms and cognitive dysfunction. This novel approach is useful for evaluating the cellular mechanisms of action of atypical antipsychotic drugs.  (+info)

BIIR 561 CL: a novel combined antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and voltage-dependent sodium channels with anticonvulsive and neuroprotective properties. (5/683)

Antagonists of glutamate receptors of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype, as well as of voltage-gated sodium channels, exhibit anticonvulsive and neuroprotective properties in vivo. One can postulate that a compound that combines both principles might be useful for the treatment of disorders of the central nervous system, like focal or global ischemia. Here, we present data on the effects of dimethyl-(2-[2-(3-phenyl-[1,2, 4]oxadiazol-5-yl)-phenoxy]ethyl)-amine hydrochloride (BIIR 561 CL) on neuronal AMPA receptors and voltage-dependent sodium channels. BIIR 561 CL inhibited AMPA receptor-mediated membrane currents in cultured cortical neurons with an IC50 value of 8.5 microM. The inhibition was noncompetitive. In a cortical wedge preparation, BIIR 561 CL reduced AMPA-induced depolarizations with an IC50 value of 10.8 microM. In addition to the effects on the glutamatergic system, BIIR 561 CL inhibited binding of radiolabeled batrachotoxin to rat brain synaptosomal membranes with a Ki value of 1.2 microM. The compound reduced sodium currents in voltage-clamped cortical neurons with an IC50 value of 5.2 microM and inhibited the veratridine-induced release of glutamate from rat brain slices with an IC50 value of 2.3 microM. Thus, BIIR 561 CL inhibited AMPA receptors and voltage-gated sodium channels in a variety of preparations. BIIR 561 CL suppressed tonic seizures in a maximum electroshock model in mice with an ED50 value of 2.8 mg/kg after s.c. administration. In a model of focal ischemia in mice, i.p. administration of 6 or 60 mg/kg BIIR 561 CL reduced the area of the infarcted cortical surface. These data show that BIIR 561 CL is a combined antagonist of AMPA receptors and voltage-gated sodium channels with promising anticonvulsive and neuroprotective properties.  (+info)

SPD 502: a water-soluble and in vivo long-lasting AMPA antagonist with neuroprotective activity. (6/683)

Accumulating preclinical data suggest that compounds that block the excitatory effect of glutamate on excitatory amino acid receptors may have neuroprotective effects and utility for the treatment of neurodegeneration after brain ischemia. In the present study, the in vitro and in vivo pharmacological properties of the novel glutamate antagonist SPD 502 [8-methyl-5(4-(N,N-dimethylsulfamoyl)phenyl)-6,7, 8,9,-tetrahydro-1H-pyrrolo[3,2-h]-isoquinoline-2, 3-dione-3-O-(4-hydroxybutyric acid-2-yl)oxime] are described. In binding studies, SPD 502 was shown to display selectivity for the [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-binding site (IC50 = 0.043 microM) compared with the [3H]kainate- (IC50 = 81 microM), [3H]cis-4-phosphonomethyl-2-piperidine carboxylic acid-(CGS 19755), and [3H]glycine-binding sites (IC50 > 30 microM) in rat cortical membranes. In an in vitro functional assay, SPD 502 blocked the AMPA-induced release of [3H]gamma-aminobutyric acid from cultured mouse cortical neurons in a competitive manner with an IC50 value of 0.23 microM. Furthermore, SPD 502 potently and selectively inhibited AMPA-induced currents in cortical neurons with an IC50 value of 0.15 microM. In in vivo electrophysiology, SPD 502 blocked AMPA-evoked spike activity in rat hippocampus after i.v. administration with an ED50 value of 6.1 mg/kg and with a duration of action of more than 1 h. Furthermore, SPD 502 increased the seizure threshold for electroshock-induced tonic seizures in mice at i.v doses of 40 mg/kg and higher. In the two-vessel occlusion model of transient forebrain ischemia in gerbils, SPD 502 (10 mg/kg bolus injection followed by a 10 mg/kg/h infusion for 2 h) resulted in a highly significant protection against the ischemia-induced damage in the hippocampal CA1 pyramidal neurons.  (+info)

Ethanol inhibition of synaptically evoked kainate responses in rat hippocampal CA3 pyramidal neurons. (7/683)

Many studies have demonstrated that intoxicating concentrations of ethanol (10-100 mM) can selectively inhibit the component of glutamatergic synaptic transmission mediated by N-methyl-D-aspartate (NMDA) receptors while having little or no effect on excitatory synaptic transmission mediated by non-NMDA receptors [i.e., alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and/or kainate (KA) receptors]. However, until the recent development of highly selective AMPA receptor antagonists, it was not possible to assess the relative contribution of AMPA and KA receptors to non-NMDA receptor-mediated synaptic transmission or to determine whether these glutamate receptor subtypes differed in their sensitivity to ethanol. In the present experiments, we used the highly selective AMPA receptor antagonist LY 303070 to pharmacologically isolate KA receptor-mediated excitatory postsynaptic currents (EPSCs) in rat hippocampal CA3 pyramidal neurons and tested their sensitivity to ethanol. Concentrations of ethanol as low as 20 mM significantly and reversibly depressed KA EPSCs. Ethanol also inhibited KA currents evoked by direct pressure application of KA in the presence of LY 303070, suggesting that this inhibition was mediated by a postsynaptic action. In contrast, ethanol had no effect on AMPA EPSCs in these cells, even at the highest concentration tested (80 mM). Ethanol significantly inhibited NMDA EPSCs in these neurons, but these responses were less sensitive to ethanol than KA EPSCs. These results suggest that in addition to its well-described depressant effect on NMDA receptor-mediated synaptic transmission, ethanol has an even greater inhibitory effect on glutamatergic synaptic transmission mediated by KA receptors in rat hippocampal CA3 pyramidal neurons.  (+info)

Differential roles of ionotropic glutamate receptors in canine medullary inspiratory neurons of the ventral respiratory group. (8/683)

The relative roles of ionotropic N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in supplying excitatory drive to inspiratory (I) augmenting pattern neurons of the ventral respiratory group were studied in anesthetized, ventilated, paralyzed, and vagotomized dogs. Multibarrel micropipettes were used to record simultaneously single-unit neuronal activity and pressure microeject the NMDA antagonist, 2-amino-5-phosphonovalerate (AP5; 2 mM), the non-NMDA antagonist 2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX; 0.25 mM), and an artificial cerebrospinal fluid vehicle. Ejected volume-rates were measured directly via meniscus level changes. The moving time average of phrenic nerve activity was used to determine respiratory phase durations and to synchronize cycle-triggered histograms of the discharge patterns. Both AP5 and NBQX produced dose-dependent reductions in peak spontaneous I neuronal discharge frequency (Fn). The average (+/- SE) maximum reduction in peak Fn produced by AP5 was 69.1 +/- 4.2% and by NBQX was 47.1 +/- 3.3%. Blockade of both glutamate receptor subtypes nearly silenced these neurons, suggesting that their activity is highly dependent on excitatory synaptic drive mediated by ionotropic glutamate receptors. Differential effects were found for the two glutamatergic antagonists. AP5 produced downward, parallel shifts in the augmenting pattern of discharge, whereas NBQX reduced the slope of the augmenting discharge pattern. These results suggest that time-varying excitatory input patterns to the canine I bulbospinal neurons are mediated by non-NMDA glutamate receptors and that constant or tonic input patterns to these neurons are mediated by NMDA receptors.  (+info)

*Licostinel

... and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-preferring receptors". Mol. Pharmacol. 49 (3): 540-6. PMID 8643094 ... 151-. ISBN 978-3-7643-6011-5. Chas Bountra; Rajesh Munglani; William K. Schmidt (28 May 2013). Pain: Current Understanding, ... Licostinel (INN) (code name ACEA-1021) is a competitive, silent antagonist of the glycine site of the NMDA receptor (Kb = 5 nM ... 249-. ISBN 978-0-306-47694-5. Wilding TJ, Huettner JE (1996). "Antagonist pharmacology of kainate- ...

*GRIA4

2003). "Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor channels lacking the N-terminal domain". J. ... The R/G site is found at amino acid 769 immediately before the 3-amino-acid-long flip and flop modules introduced by ... Ripellino JA, Neve RL, Howe JR (1998). "Expression and heteromeric interactions of non-N-methyl-D-aspartate glutamate receptor ... These channels are also responsive to the glutamate agonist, alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionate (AMPA). Some ...

*Racetam

"Nootropic drugs positively modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-sensitive glutamate receptors in ... Ahmed, A. H.; Oswald, R. E. (2010). "Piracetam Defines a New Binding Site for Allosteric Modulators of α-Amino-3-hydroxy-5- ... methyl-4-isoxazole-propionic Acid (AMPA) Receptors". Journal of Medicinal Chemistry. 53 (5): 2197-2203. doi:10.1021/jm901905j. ... 58 (4): 1199-1204. doi:10.1111/j.1471-4159.1992.tb11329.x. PMID 1372342. Vavers E, Zvejniece L, Veinberg G, Svalbe B, ...

*LY-503430

2003). "LY503430, a novel alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor potentiator with functional, ... allosteric modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors". The Journal of Pharmacology and ... 3 (3): 181-94. doi:10.2174/1568007043337508. PMID 15180479. O'neill, MJ; Witkin, JM (2007). "AMPA receptor potentiators: ...

*Strictly standardized mean difference

"Inhibition of calcineurin-mediated endocytosis and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors ... Nucleic Acids Research. 36 (14): 4667-79. doi:10.1093/nar/gkn435. PMC 2504311 . PMID 18628291. Zhang XHD (2009). "A method for ... 4 (9): e6892. doi:10.1371/journal.pone.0006892. PMC 2731218 . PMID 19727391. Malo N, Hanley JA, Carlile G, Liu J, Pelletier J, ... 10 (3): 345-58. doi:10.2217/14622416.10.3.345. PMID 20397965. Zhang XHD (2010). "Assessing the size of gene or RNAi effects in ...

*Hit selection

"Inhibition of calcineurin-mediated endocytosis and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors ... Nucleic Acids Research. 36: 4667-79. doi:10.1093/nar/gkn435. PMC 2504311 . PMID 18628291. Klinghoffer RA, Frazier J, Annis J, ... 4: e6892. doi:10.1371/journal.pone.0006892. PMC 2731218 . PMID 19727391. Zhang XHD (2010). "An effective method controlling ...

*GRIA1

The GRIA1 belongs to a family of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. Each of the members ( ... Ripellino JA, Neve RL, Howe JR (1998). "Expression and heteromeric interactions of non-N-methyl-D-aspartate glutamate receptor ... Leonard AS, Davare MA, Horne MC, Garner CC, Hell JW (July 1998). "SAP97 is associated with the alpha-amino-3-hydroxy-5- ... Leonard AS, Davare MA, Horne MC, Garner CC, Hell JW (1998). "SAP97 is associated with the alpha-amino-3-hydroxy-5- ...

*GRIK2

"Amino acid substitutions in the pore helix of GluR6 control inhibition by membrane fatty acids". J. Gen. Physiol. 132 (1): 85- ... Leuschner WD, Hoch W (1999). "Subtype-specific assembly of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor ... Ripellino JA, Neve RL, Howe JR (Jan 1998). "Expression and heteromeric interactions of non-N-methyl-D-aspartate glutamate ... The pre-mRNA of GLUR-6 is edited at three positions at amino acid positions 567, 571, and 621. The Q/R position is so called as ...

*IDRA-21

... alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor biophysics and synaptic responses" (Free full text). ... a benzothiadiazine derivative that enhances cognition by attenuating DL-alpha-amino-2,3-dihydro-5-methyl-3-oxo-4- ... isoxazolepropanoic acid (AMPA) receptor desensitization". The Journal of Pharmacology and Experimental Therapeutics. 272 (1): ... 10 (5): 1229-48. doi:10.1016/S0968-0896(01)00405-9. ISSN 0968-0896. PMID 11886787. Arai, AC; Xia, YF; Kessler, M; Phillips, D; ...

*Brain-derived neurotrophic factor

This point mutation in the coding sequence, a guanine to adenine switch at position 196, results in an amino acid switch: ... "Brain-derived neurotrophic factor regulates the expression and synaptic delivery of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic ... subunit of the N-methyl-D-aspartate receptor". The Journal of Biological Chemistry. 276 (1): 693-9. doi:10.1074/jbc.M008085200 ... The proteins resulting from mRNA that does get translated, are not trafficked and secreted normally, as the amino acid change ...

*CSPG4

Stegmüller J, Werner H, Nave KA, Trotter J (2003). "The proteoglycan NG2 is complexed with alpha-amino-3-hydroxy-5-methyl-4- ... isoxazolepropionic acid (AMPA) receptors by the PDZ glutamate receptor interaction protein (GRIP) in glial progenitor cells. ... 2005). "Phosphorylation of NG2 proteoglycan by protein kinase C-alpha regulates polarized membrane distribution and cell ... 30 (3): 408-17. doi:10.1016/j.mcn.2005.08.005. PMID 16169245. Brekke C, Lundervold A, Enger PØ, et al. (2006). "NG2 expression ...

*GRIP2

Stegmüller J, Werner H, Nave KA, Trotter J (2003). "The proteoglycan NG2 is complexed with alpha-amino-3-hydroxy-5-methyl-4- ... isoxazolepropionic acid (AMPA) receptors by the PDZ glutamate receptor interaction protein (GRIP) in glial progenitor cells. ... "The carboxyl terminus of the prolactin-releasing peptide receptor interacts with PDZ domain proteins involved in alpha-amino-3- ... hydroxy-5-methylisoxazole-4-propionic acid receptor clustering". Mol. Pharmacol. 60 (5): 916-23. PMID 11641419. ...

*NPTX2

It also plays a role in clustering of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors ... 50 (3): 329-37. doi:10.1016/j.lungcan.2005.06.011. PMID 16115696. Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status ... 31 (4): 940-3. doi:10.1016/j.pnpbp.2007.02.016. PMID 17408830. Poulsen TT, Pedersen N, Perin MS, et al. (2006). "Specific ... 35 (3): e9-15. doi:10.1097/MPA.0b013e318153fa42. PMID 17895837. Marui T, Koishi S, Funatogawa I, et al. (2007). "No association ...

*Metaplasticity

Gliotransmitters include glutamate, ATP, and, more recently, the amino acid D-serine. Once thought to be glycine itself, D- ... alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA), respectively, but they both ... A low alpha/beta ratio causes an increased threshold for cellular excitation via calcium influx and thus favors LTP. There are ... Recent research has found that the calcium-dependent enzyme CaMKII, which exists in an alpha and beta isoform, is key in ...

*GYKI-52,466

Neuron 10, 51, (1993) Wilding, T.J., Huettner, J.E., Differential antagonism of alpha-amino-3-hydroxy-5-methyl-4- ... isoxazolepropionic acid-preferring and kainate-preferring receptors by 2,3-benzodiazepines. Mol. Pharmacol. 47, 582, (1995) ... Allosteric regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors by thiocyanate and cyclothiazide at a ... Unlike conventional 1,4-benzodiazepines, GYKI-52466 and related 2,3-benzodiazepines do not act on GABAA receptors. Like other ...

*S-18986

Bourasset F, Bernard K, Muñoz C, Genissel P, Scherrmann JM (August 2005). "Neuropharmacokinetics of a new alpha-amino-3-hydroxy ... 202 (1-3): 225-35. doi:10.1007/s00213-008-1301-x. PMID 18762915. Gupta SK, Mishra R, Kusum S, Spedding M, Meiri KF, Gressens P ... 16 (4): 624-37. doi:10.1038/cdd.2008.188. PMID 19136940. Destot-Wong KD, Liang K, Gupta SK, Favrais G, Schwendimann L, Pansiot ... 19 (3): 235-44. doi:10.1097/FBP.0b013e3282feb0c1. PMID 18469541. Kelly SJ, Bernard K, Muñoz C, Lawrence RC, Thacker J, Grillo ...

*List of MeSH codes (D03)

... urocanic acid MeSH D03.383.129.385 --- isoxazoles MeSH D03.383.129.385.025 --- alpha-amino-3-hydroxy-5-methyl-4- ... isoxazolepropionic acid MeSH D03.383.129.385.162 --- cycloserine MeSH D03.383.129.385.231 --- ibotenic acid MeSH D03.383. ... pyridoxic acid MeSH D03.383.725.450 --- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine MeSH D03.383.725.463 --- metyrapone MeSH ... niflumic acid MeSH D03.066.515.635 --- pipemidic acid MeSH D03.066.515.650 --- piromidic acid MeSH D03.066.515.950 --- ...

*AMPA

... kainic acid and N-methyl-D-aspartic acid (NMDA) channels. In the synapse, these receptors serve very different purposes. AMPA ... ISBN 978-0-87893-697-7. Dinh, L; Nguyen T; Salgado H; Atzori M (2009). "Norepinephrine homogeneously inhibits alpha-amino-3- ... AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) is a compound that is a specific agonist for the AMPA receptor, ... hydroxyl-5-methyl-4-isoxazole-propionate- (AMPAR-) mediated currents in all layers of the temporal cortex of the rat". ...

*Ligand-gated ion channel

... aminocyclopropanecarboxylic acid; D-cycloserine; L-aspartate; quinolinate, etc. Partial agonists : N-methyl-D-aspartic acid ( ... Excitatory and Inhibitory Amino Acids". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical ... harboring an alpha-helix and 10 beta-strands. Following the ECD, four transmembrane segments (TMSs) are connected by ... Domoic acid, Quisqualic acid, etc. Antagonists: CNQX, Kynurenic acid, NBQX, Perampanel, Piracetam, etc. Positive allosteric ...

*CAMP-dependent pathway

The Gs alpha subunit of the stimulated G protein complex exchanges GDP for GTP and is released from the complex. In a cAMP- ... Man, Heng-Ye; Sekine-Aizawa, Yoko; Huganir, Richard L. (27 February 2007). "Regulation of α-amino-3-hydroxy-5-methyl-4- ... isoxazolepropionic acid receptor trafficking through PKA phosphorylation of the Glu receptor 1 subunit". Proceedings of the ... The Gs alpha subunit, in turn, activates adenylyl cyclase, which quickly converts ATP into cAMP. This leads to the activation ...

*AMPA receptor

A 38-amino acid sequence found prior to (i.e., before the N-terminus of) the fourth membranous domain in all four AMPAR ... Derkach V, Barria A, Soderling TR (March 1999). "Ca2+/calmodulin-kinase II enhances channel conductance of alpha-amino-3- ... hydroxy-5-methyl-4-isoxazolepropionate type glutamate receptors". Proc. Natl. Acad. Sci. U.S.A. 96 (6): 3269-74. doi:10.1073/ ... While the amino acid sequence of the subunit indicated that there seemed to be four transmembrane domains (parts of the protein ...
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TY - JOUR. T1 - Inhibition by adenosine A(2A) receptors of NMDA but not AMPA currents in rat neostriatal neurons. AU - Wirkner, Kerstin. AU - Assmann, Heike. AU - Köles, L.. AU - Gerevich, Zoltan. AU - Franke, Heike. AU - Nörenberg, Wolfgang. AU - Boehm, Rudolf. AU - Illes, Peter. PY - 2000. Y1 - 2000. N2 - 1. Whole-cell patch clamp experiments were used to investigate the transduction mechanism of adenosine A(2A) receptors in modulating N-methyl-D-aspartate (NMDA)-induced currents in rat striatal brain slices. The A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5-N-ethylcarboxamidoadenosine (CGS 21680) inhibited the NMDA, but not the (S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) current in a subset of striatal neurons. 2. Lucifer yellow-filled pipettes in combination with immunostaining of A(2A) receptors were used to identify CGS 21680-sensitive cells as typical medium spiny striatal neurons. 3. Dibutyryl cyclic AMP and the protein kinase A activator Sp-cyclic ...
Functional reconstitution of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors from rat brain. Article date: 1992/11/1 PubMed ID: 1383430 Journal name: Journal of neurochemistry (ISSN: 0022-3042) ABSTRACT Glutamate receptors belonging to the subclass specifically activated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) were solubilized from rat forebrain membranes with Triton X-100 and partially purified through a series of three chromatograph…
AMPA Receptors: A class of ionotropic glutamate receptors characterized by their affinity for the agonist AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid).
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The effects of cyclothiazide on the properties of (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors were studied using equilibrium binding techniques and interactions with other compounds known to modulate the receptors. Cyclothiazide caused a reduction in [3H]AMPA binding in assays carried out in the presence of thiocyanate, a chaotropic ion that markedly increases the affinity of AMPA receptors and accelerates their desensitization. In the absence of thiocyanate, however, cyclothiazide had no reliable effect on the binding of [3H]AMPA or on the affinity for this agonist assessed from the displacement of [3H]CNQX. The interaction of cyclothiazide with the receptor appears not to be changed by the presence of thiocyanate. Analysis of the results with a kinetic model of the AMPA receptor suggests that cyclothiazide does not block receptor desensitization by making the desensitized state inaccessible but rather by stabilizing the active state, i.e., by ...
The changes in excitatory amino acid receptor ligand binding induced by transient cerebral ischemia were studied in the rat hippocampal subfields. Ten minutes of ischemia was induced by common carotid artery occlusion combined with hypotension, and the animals were allowed variable periods of recovery ranging from 1 day to 4 weeks. The binding of 3H-AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) to quisqualate receptors, 3H-kainic acid (KA) to kainate receptors, and 3H-glutamate to N-methyl-D-aspartate (NMDA) receptors as determined by quantitative autoradiography. One week following ischemia the CA1 region of the hippocampus displayed a severe (90%) dendrosomatic lesion with preservation of presynaptic terminals. This was associated with a 60% decrease in AMPA binding and a 25% decrease in glutamate binding to NMDA receptors. At 4 weeks postischemia, both AMPA and NMDA sites were greatly reduced. Although the dentate gyrus granule cells are resistant to an ischemic insult of ...
When using this server please cite the following paper:. Zsila F, Bikadi Z, Malik D, Hari P, Pechan I, Berces A, Hazai E.. Evaluation of drug-human serum albumin binding interactions with support vector machine aided online automated docking.. Bioinformatics. 2011 May 18. ...
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Several AMPA antagonists have been developed as neuroprotective compounds and have entered clinical development. None of these compounds has reached phase 3 clinical trials, and unacceptable adverse events can be the main obstacle. The most prominent finding of this study was that the administration of the AMPA antagonist ZK200775 in ischemic stroke patients resulted in a transient neurological deterioration, which was associated with a higher than expected rise in serum S-100B levels. The level of sedation was more severe in stroke patients and occurred later than in normal subjects during the phase 1 studies. Besides a longer infusion time and higher doses in stroke patients, blood-brain barrier disruption, with increased tissue concentrations, may be responsible for these differences. Although baseline stroke characteristics were not equally distributed in all treatment groups, this is not a sufficient explanation for the difference in serum S-100B levels between the placebo group and dose ...
Ionotropic glutamatergic receptors open cation-permeable channels to mediate sodium (Na+), potassium (K+) or calcium (Ca2+) ion flow. There are three families of ionotropic receptors: the N-methyl-d-aspartate (NMDA), the amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and the kainate receptors.. The AMPA and the kainate receptors are collectively termed non-NMDA receptors and appear to control conductance of Na+ and K+ through channels that exhibit rapid kinetics. AMPA receptors are predominantly post-synaptic receptors, widely distributed in the cortex and ventral striatum and in temporal lobe structures such as the hippocampus and amygdala, with lower levels in the thalamus. Of the three ionotropic receptors in the CNS, AMPA receptors occur at the greatest density. They include GluR1, GluR2, GluR3 and GluR4. The agonists acting at AMPA receptors are AMPA and amino-3-hydroxy-5-tert-butyl-4-isoxazole propionic acid (ATPA). They mediate most fast excitatory transmissions in the ...
BioAssay record AID 92347 submitted by ChEMBL: Binding affinity by measuring displacement of [3H]AMPA from Ionotropic glutamate receptor AMPA in rat cortical slice preparation.
Excitatory glutamatergic neurotransmission at Ia afferent-motoneuron synapses is enhanced shortly after physically severing or blocking impulse propagation of the afferent and/or motoneuron axons. We considered the possibility that these synaptic changes occur because of alterations in the number or properties of motoneuron α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors. Therefore, we quantitatively analyzed glutamate receptor (GluR)1, GluR2/3, and GluR4 AMPA subunit immunoreactivity (ir) in motoneurons 3, 7, or 14 days after axotomy or continuous tetrodotoxin (TTX) block of the sciatic nerve. GluR1-ir remained low in experimental and control motoneurons with either treatment and at any date. However, there was a large reduction of GluR2/3-ir (peak at 7 days |60% reduced) and a smaller, but statistically significant, reduction of GluR4-ir (around 10% reduction at days 3, 7, and 14) in axotomized motoneurons. TTX sciatic blockade did not affect AMPA subunit immunostainings. Axonal
The novel AMPA antagonist RPR 119990 has a potent affinity for the rat AMPA receptor in membrane-binding studies that compares favorably with results for other AMPA receptor antagonists described in the literature (Takahashi et al., 1998; Turski et al., 1998). The compound was selective with respect to other ionotropic glutamate receptors, although a certain affinity for the kainate-binding site at around 50-fold higher concentrations was noted. The compound shows low or negligible affinity for 37 other binding or uptake sites, suggesting strong specificity of action. The activity on the closely related kainite site is expected, because cross-reactivity has already been reported (Bleakman and Lodge, 1998) and may account for some of the compounds anticonvulsant and neuroprotective actions.. RPR 119990 acts as a competitive antagonist at the recombinant human AMPA receptor/channel expressed in X. laevis oocytes. The compound shows a profile compatible with a competitive single site antagonism of ...
3-METHYL SUBSTITUTION ON THE 4-AMINOPHENYL MOIETY AND 8-HALOGENATION SEPARATELY INCREASE ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC ACID (AMPA) / KAINATE CHANNEL BLOCKING ABILITY OF 1-(4-AMINOPHENYL) -2, 3-BENZODIAZEPINE COMPOUNDS.. A192.36. Poster 253 - Tue 13/07, 16:45 - Hall ...
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AIM: Stroke prevalence increases with age, while alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) and inflammation have been related to ischaemia-induced damage. This study shows how age and treatment with an anti-inflammatory agent (meloxicam) modify the levels of AMPAR subunits GluR1 and GluR2, as well as the mRNA levels of the GluR2-editing enzyme ...
1M5C: Structural Basis for AMPA Receptor Activation and Ligand Selectivity: Crystal Structures of Five Agonist Complexes with the GluR2 Ligand-binding Core
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4-hydroxy-4-methyl-2,5-cyclohexadien-1-one - chemical structural formula, chemical names, chemical properties, synthesis references
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The density of N-methyl-D-aspartate (NMDA) receptors on membranes prepared from cultured cortical neurons was determined using binding assays with [125I]I-MK-801 after exposure of cultures to antagonists of the NMDA receptor complex. The density of binding sites for [125I]I-MK-801 was increased by 40-80% after exposure to D-2-amino-5-phosphonopentanoic acid (D-AP5), with no change in the number or viability of neurons. The effect of D-AP5 was concentration dependent, with an EC50 of 10 microM. Up-regulation of NMDA receptors was observed after 2-7 days but not after 1 day of exposure to 100 microM D-AP5. The density of NMDA receptors was also increased after exposure of cells to CGS 19755 and MK-801 but not after exposure to the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. The binding of [3H]AMPA was unaltered after exposure to D-AP5. These results demonstrate that the density of NMDA receptors on cultured ...
OBJECTIVE: We tested whether antibody screening samples of patients with suspected autoimmune encephalitis with additional research assays would improve the detection of autoimmune encephalitis compared with standard clinical testing alone. METHODS: We examined 731 samples (333 CSF, 182 sera, and 108 pairs) from a cohort of 623 patients who were tested for CNS autoantibodies by the University of Pennsylvania clinical laboratory over a 24-month period with cell-based assays (CBAs) on commercially obtained slides of fixed cells for antibodies to NMDA receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), γ-aminobutyric acid-B receptor (GABABR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (Caspr2), and glutamic acid decarboxylase (GAD65 ...
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Glutamate Receptor 1 (AMPA subtype)兔单克隆抗体[EPR2148](ab76321)可与小鼠, 大鼠, 人样本反应并经WB实验严格验证。所有产品均提供质保服务,中国75%以上现货。
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Drug-dependent neural plasticity related to drug addiction and schizophrenia can be modeled in animals as behavioral sensitization, which is induced by repeated noncontingent or self-administration of many drugs of abuse. Molecular mechanisms that are critical for behavioral sensitization have yet to be specified. Long-term depression (LTD) of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor (AMPAR)-mediated synaptic transmission in the brain has been proposed as a cellular substrate for learning and memory. The expression of LTD in the nucleus accumbens (NAc) required clathrin-dependent endocytosis of postsynaptic AMPARs. NAc LTD was blocked by a dynamin-derived peptide that inhibited clathrin-mediated endocytosis or by a GluR2-derived peptide that blocked regulated AMPAR endocytosis. Systemic or intra-NAc infusion of the membrane-permeable GluR2 peptide prevented the expression of amphetamine-induced behavioral sensitization in the rat. ...
In the second group of disorders, antibodies target intracellular synaptic proteins [e.g. 65?kDa glutamic acid decarboxylase (GAD65) and amphiphysin] that might be vulnerable to antibody-mediated disruption during synaptic vesicle fusion and reuptake. However, it is unclear if antibodies or T cell mechanisms mediate the neuronal dysfunction. The third and largest group, and the focus of this section, is the autoimmune encephalitis syndromes associated with antibodies to synaptic or neuronal cell-surface antigens, such as the N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or gamma-aminobutyric acid (GABA) receptors, among others (Table?1) 1. In contrast to the previously mentioned groups, which affect mainly older patients, this group of disorders frequently affect young individuals, and may occur with or without a cancer association. Prior to the elucidation of the underlying immune pathogenesis, many of these disorders were known by descriptive ...
The inhibitory potencies at excitatory amino acid (EAA) receptors of 11 quinoxaline derivatives were evaluated in two-electrode voltage-clamp recordings of Xenopus oocytes injected with rat cortex mRNA. Currents activated by kainate or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) in Xenopus oocytes were inhibited competitively by all the quinoxaline derivatives, with apparent Ki values ranging from 0.27 to 300 microM against kainate and from 0.25 to 137 microM against AMPA. An excellent correlation was observed between inhibitory potencies of the quinoxaline derivatives against kainate and AMPA currents, in support of the contention that in this preparation these two agonists act at a single site. All 11 quinoxaline derivatives also inhibited current activated by the combination of glycine and N-methyl-D-aspartate (NMDA), apparently acting at the glycine site, and did so over a narrower range of apparent Ki values (0.37-8.1 microM). The correlation between the ...
Our findings suggest opposing actions of Narp and NP1 versus NPR in cocaine-induced plasticity that parallel their differential actions in synaptogenesis and excitatory transmission. Narp and NP1 are able to multimerize and promote clustering of AMPAR (OBrien et al., 2002; Xu et al., 2003), whereas NPR is thought to bind to the Narp/NP1/AMPA clusters and promote internalization of the clustered receptors (Cho et al., 2008). Consistent with a shared AMPAR clustering function for Narp and NP1, deletion of either NP caused similar alterations in spontaneous and cocaine-induced behavior and desensitized the motor response elicited by stimulating AMPAR in the nucleus accumbens. Thus, although both Narp and NP1 deletion promoted cocaine-induced place preference, NPR deletion was without effect. Narp or NP1 deletion inhibited AMPA-induced locomotion, whereas NPR deletion potentiated the motor effect of AMPA. In addition, although Narp and NP1 KO showed reduced time in the center of a novel ...
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1-(quinoxalin-6-ylcarbonyl)piperidine: modulates AMPA receptor desensitization ; an analog of 1-(1,3-benzodioxol-5-ylcarbonyl)piperidine
OGD-induced increase in AMPA receptor rectification is blocked by inhibiting PICK1 PDZ domain interactions. Top panels, example traces recorded at -70 mV and
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Catalog No. : P080102 Product Name : Maleimide-PEG2-propionic acid Synonyms : Maleimide-NH-PEG2-CH2CH2COOH CAS# : 756525-98-1 M.F. : C14H20N2O7 M.W. : 328.32 Purity : |98% Packing Size : 250mg,1g,5g,25g,100g,1kg Appearance : Liquid or Solid ...
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BioAssay record AID 91470 submitted by ChEMBL: Displacement of [3H]CNQX from Ionotropic glutamate receptor kainate/Ionotropic glutamate receptor AMPA in rat cortical membranes.
This study provides strong evidence that influx of calcium ions, particularly through Ca2+-permeable AMPA/kainate receptors and to a lesser extent voltage-gated calcium channels, is a key mediator in the ability of glutamatergic neurotransmission to potentiate the toxicity of SOD-1 mutants. JSTX-3, a specific inhibitor of Ca2+-permeable AMPA receptors, (Blaschke et al., 1993; Iino et al., 1996), was almost as effective as CNQX, a general AMPA/kainate receptor antagonist, in preventing motor neuron death induced by G93A mSOD-1 and precipitation of the mutant protein into aggregates. Because JSTX-3 does not block calcium-permeable kainate receptors, our experiments do not exclude their contribution to mSOD-1 toxicity; however, the almost complete rescue of motor neurons from cell death after treatment with JSTX-3 suggests that AMPA receptor activation was the major contributor. Moreover, the results with JSTX-3 confirm that cultured motor neurons express Ca2+-permeable AMPA/low-affinity kainate ...
Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific phosphatase that modulates key signaling molecules involved in synaptic plasticity and neuronal function. Targets include extracellular-regulated kinase 1 and 2 (ERK1/2), stress-activated protein kinase p38 (p38), the Src family tyrosine kinase Fyn, N-methyl-d-aspartate receptors (NMDARs), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). STEP-mediated dephosphorylation of ERK1/2, p38, and Fyn leads to inactivation of these enzymes, whereas STEP-mediated dephosphorylation of surface NMDARs and AMPARs promotes their endocytosis. Accordingly, the current model of STEP function posits that it opposes long-term potentiation and promotes long-term depression. Phosphorylation, cleavage, dimerization, ubiquitination, and local translation all converge to maintain an appropriate balance of STEP in the central nervous system. Accumulating evidence over the past decade indicates that STEP dysregulation ...
OBJECTIVE: We tested whether antibody screening samples of patients with suspected autoimmune encephalitis with additional research assays would improve the detection of autoimmune encephalitis compared with standard clinical testing alone. METHODS: We examined 731 samples (333 CSF, 182 sera, and 108 pairs) from a cohort of 623 patients who were tested for CNS autoantibodies by the University of Pennsylvania clinical laboratory over a 24-month period with cell-based assays (CBAs) on commercially obtained slides of fixed cells for antibodies to NMDA receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), γ-aminobutyric acid-B receptor (GABABR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (Caspr2), and glutamic acid decarboxylase (GAD65 ...
The number and type of receptors present at the postsynaptic membrane determine the response to the neurotransmitter released from the presynaptic terminal. Because most neurons receive multiple and distinct synaptic inputs and contain several different subtypes of receptors stimulated by the same neurotransmitter, the assembly and trafficking of receptors in neurons is a complex process involving many levels of regulation. To investigate the mechanism that neurons use to regulate the assembly of receptor subunits, we studied a GluR2 knock-out mouse. GluR2 is a critical subunit that controls calcium permeability of AMPA receptors and is present in most native AMPA receptors. Our data indicate that in the absence of GluR2, aberrant receptor complexes composed of GluR1 and GluR3 are formed in the hippocampus, and that there is an increased number of homomeric GluR1 and GluR3 receptors. We also show that these homomeric and heteromeric receptors are less efficiently expressed at the synapse. Our results
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article{b7673db3-71f6-4e07-ad30-abedb3a063d3, abstract = {The Fourier transform gas-phase IR spectrum of isoxazole, C3H3NO, between 550 and 1700 cm(-1) was measured with a resolution of ca. 0.003 cm(-1). Ten fundamental bands in the region 800-1700 cm(-1) have been analyzed by the Watson Hamiltonian model to yield upper state spectroscopic constants. A number of local resonances have been identified in the bands and explained qualitatively, and the unobserved nu(14)(A) fundamental band has been located at 897.5(5) cm(-1) from its perturbation effects on the neighboring fundamentals.}, author = {Hegelund, F and Wugt Larsen, René and Nicolaisen, F M and Palmer, M H}, issn = {0022-2852}, keyword = {fundamental bands,isoxazole,infrared,rotational constants}, language = {eng}, number = {2}, pages = {244--256}, publisher = {Elsevier}, series = {Journal of Molecular Spectroscopy}, title = {The high-resolution infrared spectrum of isoxazole vapor between 800 and 1700 cm(-1)}, url = ...
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Long-term potentiation (LTP) of excitatory synaptic transmission has long been considered a cellular correlate for learning and memory. Early LTP (eLTP, ,1 hour) had initially been explained either by presynaptic increases in glutamate release or by direct modification of post-synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) function. Compelling models have more recently proposed that synaptic potentiation can occur by the recruitment of additional post-synaptic AMPARs, sourced either from an intracellular reserve pool by exocytosis or from nearby extra synaptic receptors pre-existing on the neuronal surface. However, the exact mechanism through which synapses can rapidly recruit new AMPARs during eLTP is still unknown. In particular, direct evidence for a pivotal role of AMPAR surface diffusion as a trafficking mechanism in synaptic plasticity is still lacking. Using AMPAR immobilization approaches, we show that interfering with AMPAR surface diffusion ...
Decreased expression of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-preferring non-N-methyl-D-aspartate (non-NMDA) glutamate receptors (GluRs) occurs in the medial temporal lobe of schizophrenics in terms of reduced abundance of GluR1 and GluR2 subunit mRNAs. To investigate further these receptors in schizophrenia, we have performed a quantitative immunoautoradiographic study in medial temporal lobe sections of 11 schizophrenics and 10 well-matched controls. GluR1 and GluR2/3 were detected with polyclonal antisera coupled to 35S-labeled secondary antibodies. Both subunits were vulnerable to a prolonged postmortem interval and poor agonal state as indicated by brain pH. GluR1 also tended to decline with increasing age. These factors were therefore used as covariates. GluR1 abundance was reduced in schizophrenics in parahippocampal gyrus (p | .025), while GluR2/3 was lower in most subfields in the schizophrenics, significantly so in CA4 (p | .02). The present data extend the evidence
Absence epilepsy, characterized by spike-wave discharges (SWD) in the electroencephalogram, arises from aberrations within the circuitry of the cerebral cortex and thalamus that regulates awareness. The inbred mouse strain C3H/HeJ is prone to absence seizures, with a major susceptibility locus, spkw1, accounting for most of the phenotype. Here we find that spkw1 is associated with a hypomorphic retroviral-like insertion mutation in the Gria4 gene, encoding one of the four amino-3-hydroxy-5-methyl-4isoxazolepropionic acid (AMPA) receptor subunits in the brain. Consistent with this, Gria4 knockout mice also have frequent SWD and do not complement spkw1. In contrast, null mutants for the related gene Gria3 do not have SWD, and Gria3 loss actually lowers SWD of spkw1 homozygotes. Gria3 and Gria4 encode the predominant AMPA receptor subunits in the reticular thalamus, which is thought to play a central role in seizure genesis by inhibiting thalamic relay cells and promoting rebound burst firing
Definition of propionic acid in the Legal Dictionary - by Free online English dictionary and encyclopedia. What is propionic acid? Meaning of propionic acid as a legal term. What does propionic acid mean in law?
We have investigated the effect of "type":"entrez-nucleotide","attrs":"text":"U73122″,"term_id":"4098075″,"term_text":"U73122″U73122, a specific inhibitor of phospholipase C (PLC), on acetylcholine-activated K+ currents (IKACh) in mouse atrial myocytes. concentration of "type":"entrez-nucleotide","attrs":"text":"U73122″,"term_id":"4098075″,"term_text":"U73122″U73122. When KACh channels were directly activated by adding 1?mM GTPS to the bath solution in inside-out patches, "type":"entrez-nucleotide","attrs":"text":"U73122″,"term_id":"4098075″,"term_text":"U73122″U73122 (1?M) decreased the open probability significantly without change in mean open… Continue reading We have investigated the effect of "type":"entrez-nucleotide","attrs":"text":"U73122″,"term_id":"4098075″,"term_text":"U73122″U73122, a specific inhibitor of. ...
Blaschke, M.; Keller, B. U.; Rivosecchi, R.; Hollmann, M.; Heinemann, S. H.; Konnerth, A.: A single amino acid determines the subunit-specific spider toxin block of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor channels. Proceedings of the National Academy of Sciences of the United States of America 90 (14), S. 6528 - 6532 (1993 ...
Reaktivität: Fledermaus, Rind (Kuh), Hund and more. 74 verschiedene GRIK5 Antikörper vergleichen. Alle direkt auf antikörper-online bestellbar!
Mibampator, an AMPA receptor potentiator, was in phase II development with Eli Lilly for the treatment agression and agitation in patients with Alzheimers
You are viewing an interactive 3D depiction of the molecule 1-[(2s,4s,17r,18r,19s,21r,37z)-19-hydroxy-5,15,22,32-tetraazanonacyclo[18.10.10.0~1,21~.0~2,18~.0~5,17~.0~8,16~.0~9,14~.0~20,32~.0~22,30~]tetraconta-8(16),9,11,13,37-pentaen-4-yl]acetone (C39H95N4O2) from the PQR.
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Overactivation of ionotropic glutamate receptors in oligodendrocytes induces cytosolic Ca2+ overload and excitotoxic death, a process that contributes to demyelination and multiple sclerosis. Excitotoxic insults cause well-characterized mitochondrial alterations and endoplasmic reticulum (ER) dysfunction, which is not fully understood. In this study, we analyzed the contribution of ER-Ca2+ release through ryanodine receptors (RyRs) and inositol triphosphate receptors (IP(3)Rs) to excitotoxicity in oligodendrocytes in vitro. First, we observed that oligodendrocytes express all previously characterized RyRs and IP(3)Rs. Blockade of Ca2+-induced Ca2+ release by TMB-8 following alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor-mediated insults attenuated both oligodendrocyte death and cytosolic Ca2+ overload. In turn, RyR inhibition by ryanodine reduced as well the Ca2+ overload whereas IP3R inhibition was ineffective. Furthermore, AMPA-triggered mitochondrial membrane ...
Both TAR DNA binding protein of 43kDa (TDP-43) pathology and failure of RNA editing at the glutamine/arginine (Q/R) site of GluA2, a subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, are the characteristic etiology-linked molecular abnormalities that concomitantly occur in the motor neurons of the majority of patients with amyotrophic lateral sclerosis (ALS), the most common adult-onset fatal motor neuron disease. Adenosine deaminase acting on RNA 2 (ADAR2) specifically catalyzes RNA editing at the Q/R site of GluA2, and conditional ADAR2 knockout mice (ADAR2flox/flox/VAChT-Cre.Fast ; AR2 mice) exhibit a progressive ALS phenotype with TDP-43 pathology-like TDP-43 mislocalization in the ADAR2-lacking motor neurons. Because Ca2+-permeable AMPA receptor-mediated mechanism underlies death of motor neurons in the AR2 mice, amelioration of exaggerated Ca2+ influx by AMPA receptor antagonists may be a potential ALS therapy. Here we showed that oral perampanel, a selective
Song, S. H., & Augustine, G. J. (2016). Synapsin isoforms regulating GABA release from hippocampal interneurons. The Journal of Neuroscience, 36(25), 6742-6757. PMID: 27335405. Wahba, G., Hebert, A. E., Grynspan, D., Staines, W., & Schock, S. (2016). A rapid and efficient method for dissociated cultures of mouse myenteric neurons. Journal of neuroscience methods, 261, 110-116. PMID: 26706461. Magupalli, V. G., Mochida, S., Yan, J., Jiang, X., Westenbroek, R. E., Nairn, A. C., Scheuer, T. & Catterall, W. A. (2013). Ca2+-independent activation of Ca2+/calmodulin-dependent protein kinase II bound to the C-terminal domain of CaV2. 1 calcium channels. Journal of Biological Chemistry, 288(7), 4637-4648. PMID: 23255606. Kurtis D. Davies, Susan M. Goebel-Goody, Steven J. Coultrap, and Michael D. Browning (2008) Long Term Synaptic Depression That Is Associated with GluR1 Dephosphorylation but Not-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA)Receptor Internalization J. Biol. Chem., 283: 33138 ...
We are interested in understanding how kainate receptors, a family of ionotropic glutamate receptors in the mammalian CNS, operate at a molecular and biophysical level. Kainate receptors are modulatory proteins that help to balance excitatory and inhibitory tone through diverse actions at pre- and postsynaptic sites. They also have been shown to be promising drug targets in several pathologies (particularly epilepsy and chronic pain). A current project focuses on how an associated family of auxiliary proteins, known as Neto-1 and Neto-2, shape kainate receptor function. We would like to identify which domains in both the receptor subunits and auxiliary proteins are key for allosteric modulation by Neto proteins ...
Catalysis of the transmembrane transfer of an ion by a channel that opens when glutamate has been bound by the channel complex or one of its constituent parts.
... , Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
Hello, May I suggest that you use NBQX which has 2 main advantages 1. Soluble in water at 1mM concentration 2. More selective AMPA receptors antagonist (CNQX at , 10 uM concentration is a week NMDA antagonist You could get it from Tocris Cookson, UH, Fax +44 1934 853435 Hope it will help Etienne Pralong epralong at iphysiol.unil.ch ...
Lorem ipsum dolor sit amet, consectetur adipisicing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat. Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum.. Lorem ipsum dolor sit amet, consectetur adipisicing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat. Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum.. ...
吝唑(Pyrazole)和異噁唑(Isoxazole)化合物及其衍生物是許多天然物、藥物、抗生素、抗菌劑、殺蟲劑、除草劑、染料的基本架構,雖然有許多此類的雜環化合物的合成研究被報導過,但由於合成步驟繁瑣、方法及策略困難度高,常導致其合成在醫學及藥學的應用有許多限制與不便,因此我們提出一簡捷便利及具高幾何選擇性的合成方法來合成此類型化合物。我們利用丙二烯酮化合物與親核劑聯胺鹽類(H2N-NH2.2HCl)化合物於甲醇鈉(NaOMe)及二甲基醯胺(DMF)中進行加成和環化反應,可生成高產率的吝唑化合物;另一部分也是利用丙二烯酮化合物與親核劑羥胺鹽類(HO-NH2.HCl)化合物於碳酸銫(Cs2CO3)及二甲基亞碴(DMSO)中進行加成和環化反應,即生成單一幾何選擇產物的異噁唑化合物。我們亦證實反應的反應機構是親核劑(H2N-X, X = ...
Structure, properties, spectra, suppliers and links for: (3β,5ξ,12α,17α)-12-Hydroxy-28-oxo-13,28-epoxyoleanan-3-yl 3-O-β-D-xylopyranosyl-β-D-glucopyranos.
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New for the 2016 legislative session: The 43rd annual California Environmental Scorecard rates elected officials on 2016, another successful year for the environment in spite of heavy opposition from polluting industry.. Find out how your legislators did in 2016 in CLCVs California Environmental Scorecard.. ...
Ananth, C., Dheen, S.T., Gopalakrishnakone, P., Kaur, C. (2003). Distribution of NADPH-diaphorase and expression of nNOS, N-Methyl-D-Aspartate receptor (NMDAR1) and Non-NMDA glutamate receptor (GlutR2) genes in the neurons of the hippocampus after domoic acid-induced lesions in adult rats. Hippocampus 13 (2) : 260-272. [email protected] Repository. https://doi.org/10.1002/hipo. ...
It is now well established that glial cells, like neurons, express a large variety of non-NMDA glutamate receptors. However, knowledge about the subunits forming the receptors and the types of glial cells which express them is incomplete. The aim of this study was to determine the presence and distribution of kainate-preferring glutamate receptor subunits in glial cells in the white matter of adult cattle. To this end, reverse transcription and polymerase chain reaction (RT-PCR) analysis of mRNA extracted from the corpus callosum, fornix and optic nerve of brains of adult cattle was carried out using specific primers that allowed selective amplification of the kainate transcripts encoding the GluR5, GluR6, GIuR7, KAI and KA2 subunits. In the three areas studied, transcripts for all five subunits were detected. Restriction digestion of the amplified products confirmed the specificity of the PCR amplifications and showed that the extent of Q/R editing in the GluR6 subunit was lower than that ...
Cerebellar granule cell-specific deletion of the AMPA receptor subunit GluR-D gene [Elektronische Ressource] / presented by Jing Chen : DISSERTATION submitted to the Combined Faculties for the Natural Sciences and for Mathematics of the Ruperto-Carola University of Heidelberg, Germany for the degree of Doctor of Natural Sciences presented by Biologist Jing Chen born in Tangshan, China oral examination: ………………………… Cerebellar granule cell-specific deletion of the AMPA receptor subunit
3.0.CO;2-G. PMC 3501957 . PMID 10967549. Iida J, Pei D, Kang T, et al. (2001). "Melanoma chondroitin sulfate proteoglycan regulates matrix metalloproteinase-dependent human melanoma invasion into type I collagen". J. Biol. Chem. 276 (22): 18786-94. doi:10.1074/jbc.M010053200. PMID 11278606. Staub E, Hinzmann B, Rosenthal A (2002). "A novel repeat in the melanoma-associated chondroitin sulfate proteoglycan defines a new protein family". FEBS Lett. 527 (1-3): 114-8. doi:10.1016/S0014-5793(02)03195-2. PMID 12220645. Stegmüller J, Werner H, Nave KA, Trotter J (2003). "The proteoglycan NG2 is complexed with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by the PDZ glutamate receptor interaction protein (GRIP) in glial progenitor cells. Implications for glial-neuronal signaling". J. Biol. Chem. 278 (6): 3590-8. doi:10.1074/jbc.M210010200. PMID 12458226. Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length ...
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Doctor, i-force recently produced a supplement with NMDA (30mg), named Intimidate, but I wonder whether this is safe? There is likely to change
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S)-AMPA [(S)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid] - Science PROS)-AMPA [(S)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid] - Science PRO

S)-AMPA [(S)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid]. Código:. ALX-550-016 ... S)-AMPA [(S)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid] ... S)-AMPA [(S)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid] ... S)-AMPA [(S)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid] https://www.sciencepro.com.br/produtos/alx-550-016 https ...
more infohttps://www.sciencepro.com.br/produtos/alx-550-016

Inhibition of [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid binding by the excitotoxin beta-N-oxalyl-L-alpha...Inhibition of [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid binding by the excitotoxin beta-N-oxalyl-L-alpha...

... beta-diaminopropionic acid. Article date: 1988/1/19 PubMed ID: 2895006 Journal name: European journal of pharmacology (ISSN: ... alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid binding by the excitotoxin beta-N-oxalyl-L-alpha, ... N-Methyl-D-Aspartate; Receptors, Neurotransmitter; Toxins, Biological; oxalyldiaminopropionic acid; Ibotenic Acid; alpha-Amino- ... Kainic Acid, oxalyldiaminopropionic acid, Oxadiazoles, Oxazoles, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, ...
more infohttps://muscimol.xyz/2895006

Solubilization, characterization, and partial purification of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-,...Solubilization, characterization, and partial purification of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-,...

... and partial purification of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-, quisqualate-, kainate-sensitive L- ... Substances mentioned in the article: Detergents; Glutamates; Ibotenic Acid; Polyethylene Glycols; Glutamic Acid; alpha-Amino-3- ... Kainic Acid/pharmacology; Polyethylene Glycols; Quisqualic Acid/pharmacology; Solubility; Synapses/metabolism; alpha-Amino-3- ... Quisqualic Acid, Detergents, Glutamates, Nonidet P-40, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Kainic Acid, ...
more infohttps://muscimol.xyz/1682417

RCSB PDB 









for 1MY2RCSB PDB for 1MY2

... studies of 5-substituted willardiines and GluR2 S1S2 in the crystal. ... S)-ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC ACID. AMPA (Synonym). C7 H10 N2 O4 UUDAMDVQRQNNHZ-YFKPBYRVSA-N ... Version 1_4: 2017-08-23. Type: Refinement description, Source and taxonomy ...
more infohttp://www.rcsb.org/pdb/explore/biologyAndChemistry.do?structureId=1MY2

Fish and chips: functional genomics of social plasticity in an African cichlid fish | Journal of Experimental BiologyFish and chips: functional genomics of social plasticity in an African cichlid fish | Journal of Experimental Biology

N-methyl-D-aspartic acid. POA. pre-optic area. POMC. proopiomelanocortin. RI. reproductive index. T. testosterone. TC. ... alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid. AVP. arginine vasopressin. AVT. arginine vasotocin. BPP. Bayesian ... The role of amino acid neurotransmitters in the regulation of pituitary gonadotropin release in fish. Biochem. Cell Biol. 78, ... gamma-aminobutyric acid. GH. growth hormone. GHRH. growth hormone-releasing hormone. GnRH. gonadotrophin-releasing hormone. GO ...
more infohttp://jeb.biologists.org/content/211/18/3041.long

Regulation of endosomal motility and degradation by amyotrophic lateral sclerosis 2/alsin.  - White Rose Research Online
		Regulation of endosomal motility and degradation by amyotrophic lateral sclerosis 2/alsin. - White Rose Research Online

... alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; rab5 GTP-Binding Proteins. ... White Rose Research Online is powered by EPrints 3 which is developed by the School of Electronics and Computer Science at the ... 3 more authors) (2009) Regulation of endosomal motility and degradation by amyotrophic lateral sclerosis 2/alsin. Molecular ...
more infohttp://eprints.whiterose.ac.uk/80826/

Dodging the cognitive hit of early-life seizures - Healthcanal.com : Healthcanal.comDodging the cognitive hit of early-life seizures - Healthcanal.com : Healthcanal.com

AMPA stands for alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid.) ... All these changes were evident within 2-3 days after the seizure. ...
more infohttps://www.healthcanal.com/brain-nerves/24679-dodging-the-cognitive-hit-of-early-life-seizures.html

Differences and diversity of autoimmune encephalitis in 77 cases from a single tertiary care center | Springer for Research &...Differences and diversity of autoimmune encephalitis in 77 cases from a single tertiary care center | Springer for Research &...

alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. ANNA. anti-neuronal nuclear antibody ... Human N-methyl D-aspartate receptor antibodies alter memory and behaviour in mice. Brain. 2015;138(Pt 1):94-109.PubMedCrossRef ... gamma-aminobutyric acid receptor. GAD. glutamic acid decarboxylase. GFAP. Glial Fibrillary Acidic Protein ... Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol. 2009;66(1):11-8.PubMed ...
more infohttps://rd.springer.com/article/10.1186%2Fs12883-019-1501-5

The Dynamic Effects of Nicotine on the Developing BrainThe Dynamic Effects of Nicotine on the Developing Brain

alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor. G. gestational day. GABA. Gamma-aminobutyric acid ... N- methyl D-aspartate glutamate receptor. P. postnatal day. SIDS. sudden infant death syndrome. SN. substantia nigra. VTA. ... Belhage B, Hansen GH, Elster L, Schousboe A. Effects of gamma-aminobutyric acid (GABA) on synaptogenesis and synaptic function ... Localization of alpha 7 nicotinic receptor subunit mRNA and alpha-bungarotoxin binding sites in developing mouse somatosensory ...
more infohttp://pubmedcentralcanada.ca/pmcc/articles/PMC2746456/

Frontiers | Development of inflammation-induced hyperalgesia and allodynia is associated with the upregulation of extrasynaptic...Frontiers | Development of inflammation-induced hyperalgesia and allodynia is associated with the upregulation of extrasynaptic...

This upregulation was manifested as a robust increase in the amplitude of AMPAR-mediated currents 2-3 h post-CFA. These changes ... This upregulation was manifested as a robust increase in the amplitude of AMPAR-mediated currents 2-3 h post-CFA. These changes ... we showed that remarkable hyperalgesia and allodynia developes in 1-3 h after intraplantar CFA injection. By utilizing patch- ... we showed that remarkable hyperalgesia and allodynia developes in 1-3 h after intraplantar CFA injection. By utilizing patch- ...
more infohttps://www.frontiersin.org/articles/10.3389/fphys.2012.00391/full

Gene InfoGene Info

CC] alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid selective glutamate receptor complex *[CC] endocytic vesicle ... BP] regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity *[BP] synaptic ... calcium channel, voltage-dependent, gamma subunit 4. 3837002. Incomplete. BC004504. calcium channel, voltage-dependent, gamma ...
more infohttps://cgap.nci.nih.gov/Genes/GeneInfo?ORG=Hs&CID=514423

Gene InfoGene Info

CC] alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid selective glutamate receptor complex *[CC] cell junction *[CC] ... BP] regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity *[BP] regulation ...
more infohttps://cgap.nci.nih.gov/Genes/GeneInfo?ORG=Hs&CID=437072&LLNO=254263

Frontiers | A Process for Digitizing and Simulating Biologically Realistic Oligocellular Networks Demonstrated for the Neuro...Frontiers | A Process for Digitizing and Simulating Biologically Realistic Oligocellular Networks Demonstrated for the Neuro...

... alpha-amino-3-Hydroxy-5-methyl-4-isoxazole propionic acid - type glutamate ionotropic receptor; O2, molecular oxygen; H2O, ... excitatory amino acid transporter (for glutamate); Na/K ATPase, ATP-dependent sodium-potassium pump; MCT, monocarboxylate ... but midway through byproducts are shunted away and denied further processing in the oxidative tricarboxylic acid cycle (TCA) ( ... Marco Agus3,4, Daniya Boges2, Marwan Abdellah1, Kalpana Kare2, Heikki Lehväslaiho2,5, Stefan Eilemann1, Renaud Blaise Jolivet6, ...
more infohttps://www.frontiersin.org/articles/10.3389/fnins.2018.00664/full

Plus itPlus it

2002) Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor channels lacking the N-terminal domain. J Biol ... Here, we find that AMPAR subunits lacking M4 or containing single amino acid substitutions in the specific M4 face no longer ... 2007) N-Methyl-D-aspartate (NMDA) receptor subunit NR1 forms the substrate for oligomeric assembly of the NMDA receptor. J Biol ... we find that subunits lacking M4 or containing single amino acid substitutions along an "interacting" face of the M4 helix that ...
more infohttp://www.jneurosci.org/content/33/23/9840

Presynaptic and Postsynaptic Amplifications of Neuropathic Pain in the Anterior Cingulate Cortex | Journal of NeurosciencePresynaptic and Postsynaptic Amplifications of Neuropathic Pain in the Anterior Cingulate Cortex | Journal of Neuroscience

1996) Block of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by polyamines and polyamine toxins. J ... 2007) Genetic evidence for adenylyl cyclase 1 as a target for preventing neuronal excitotoxicity mediated by N-methyl-d- ... 1996) Correlation between kinetics and RNA splicing of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in ... 3A,B). We tested the time required for peak amplitude of NMDA receptor-mediated EPSCs to decay to 50% of initial value in the ...
more infohttp://www.jneurosci.org/content/28/29/7445.long

Epilepsy and Seizures Medication: Anticonvulsants, Other, Anticonvulsants, Barbiturates, Anticonvulsants, Benzodiazepine,...Epilepsy and Seizures Medication: Anticonvulsants, Other, Anticonvulsants, Barbiturates, Anticonvulsants, Benzodiazepine,...

Perampanel is a noncompetitive antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate ... Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med. 2010 Mar 4. 362(9):790-9. [Medline]. ... This agent has multiple mechanisms of action, including (1) inhibition of N-methyl-D-aspartate (NMDA)-associated sodium ... Ramon Diaz-Arrastia, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, ...
more infohttps://emedicine.medscape.com/article/1184846-medication

Simple Partial Seizures Medication: AnticonvulsantsSimple Partial Seizures Medication: Anticonvulsants

Perampanel is a noncompetitive antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate ... This is a branched-chain fatty acid that undergoes oxidative metabolism and is highly protein bound. The amount of protein ... Tiagabine is a gamma-aminobutyric acid (GABA) reuptake inhibitor, with its metabolism enhanced by cytochrome P-450 inducers. It ... It is available as a 125-mg/5 mL suspension; 50-mg chewable tablet; 30-mg capsules; 100-mg capsules; and 50-mg/mL injectable ...
more infohttps://emedicine.medscape.com/article/1184384-medication

Piracetam and Piracetam-Like Drugs | SpringerLinkPiracetam and Piracetam-Like Drugs | SpringerLink

Nootropic drugs positively modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-sensitive glutamate receptors in ... Nefiracetam potentiates N-methyl-D-aspartate (NMDA) receptor function via protein kinase C activation and reduces magnesium ... Nebracetam (WEB 1881FU) prevents N-methyl-D-aspartate receptor-mediated neurotoxicity in rat striatal slices. Jpn J Pharmacol ... 5.. Wheble PC, Sena ES, Macleod MR. A systematic review and meta-analysis of the efficacy of piracetam and piracetam-like ...
more infohttps://link.springer.com/article/10.2165%2F11319230-000000000-00000

In vivo effects of antibodies from patients with anti-NMDA receptor encephalitis: further evidence of synaptic glutamatergic...In vivo effects of antibodies from patients with anti-NMDA receptor encephalitis: further evidence of synaptic glutamatergic...

N-methyl-D-aspartate. AMPA: alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid ... In addition, we studied the effects of infusion of GABA (gamma-amino-butyric acid) after blockade of the alpha2-delta subunit ... We evaluated the effects of NMDA-R Ab on the NMDA- and AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)- ... Antibodies to the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor have been identified in a newly-described ...
more infohttps://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-31

AMPA Receptors
      - AMPA Receptor
     Summary Report | CureHunterAMPA Receptors - AMPA Receptor Summary Report | CureHunter

Amino Acids, Peptides, and Proteins*Proteins: 90489*Carrier Proteins: 11456*Membrane Transport Proteins: 165*Ion Channels: 3653 ... A class of ionotropic glutamate receptors characterized by their affinity for the agonist AMPA (alpha-amino-3-hydroxy-5-methyl- ... hydroxy- 5- methyl- 4- isoxazolepropionic Acid (AMPA) 4. Glutamic Acid (Glutamate) ... Amino Acid Receptors: 22*Glutamate Receptors: 2226*Ionotropic Glutamate Receptors: 173*AMPA Receptors: 888*glutamate receptor ...
more infohttp://www.curehunter.com/public/keywordSummaryD018091-AMPA-Receptors-AMPA-Receptor.do

Glutamate Receptors
      - Glutamate Receptor
     Summary Report | CureHunterGlutamate Receptors - Glutamate Receptor Summary Report | CureHunter

Glutamate receptors include ionotropic receptors (AMPA, kainate, and N-methyl-D-aspartate receptors), which directly control ... Excitatory Amino Acid Receptor; Receptor, Glutamate; Excitatory Amino Acid Receptors; Receptors, Excitatory Amino Acid ... human alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptor ... Glutamate receptors include ionotropic receptors (AMPA, kainate, and N-methyl-D-aspartate receptors), which directly control ...
more infohttp://www.curehunter.com/public/keywordSummaryD017470.do

Peripheral neuropathy in limbic encephalitis with anti‐glutamate receptor antibodies: Case report and systematic literature...Peripheral neuropathy in limbic encephalitis with anti‐glutamate receptor antibodies: Case report and systematic literature...

... isoxazolepropionic acid (AMPA) receptor and N‐methyl‐d‐aspartate (NMDA) receptor are known to be the causes of autoimmune ... Alphaamino3hydroxy5methyl4isoxazolepropionic acid (AMPA) and N‐methyl‐d‐aspartate (NMDA) receptors are two major ... hydroxy5methyl4isoxazolepropionic acid receptor: Case series and review of the literature. JAMA Neurology, 72(10), 1163- ... AMPA, alphaamino3hydroxy5methyl4isoxazolepropionic acid; NMDA, N‐methyl‐ ... ...
more infohttp://pubmedcentralcanada.ca/pmcc/articles/PMC5607545/

Schoepfer R[au] - PubMed - NCBISchoepfer R[au] - PubMed - NCBI

Subunit dependencies of N-methyl-D-aspartate (NMDA) receptor-induced alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ( ... Identification of amino acid residues of the NR2A subunit that control glutamate potency in recombinant NR1/NR2A NMDA receptors ... Studying block in cloned N-methyl-D-aspartate (NMDA) receptors.. Ruppersberg JP, Mosbacher J, Günther W, Schoepfer R, Fakler B. ... Subcellular localisation of recombinant alpha- and gamma-synuclein.. Specht CG, Tigaret CM, Rast GF, Thalhammer A, Rudhard Y, ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed?cmd=search&term=Schoepfer+R%5Bau%5D&dispmax=50

New Analyses Evaluate Long-Term Convulsive Seizure Freedom Rates With Use Of Adjunctive FYCOMPA® (perampanel) CIII In Adult...New Analyses Evaluate Long-Term Convulsive Seizure Freedom Rates With Use Of Adjunctive FYCOMPA® (perampanel) CIII In Adult...

FYCOMPA, a unique oral medication, is a selective, non-competitive AMPA (alpha-amino-3-hydroxy-5- methyl-4-isoxazolepropionic ... acid) receptor antagonist. The precise mechanism by which FYCOMPA exerts its antiepileptic effects in humans is unknown. In a ... Monday, December 3, 12:00 p.m. to 2:00 p.m. Study 311: Safety and efficacy of adjunctive FYCOMPA (perampanel) in pediatric ... Monday, December 3, 12:00 p.m. to 2:00 p.m. Study 311: Safety and efficacy of adjunctive FYCOMPA (perampanel) in pediatric ...
more infohttps://www.biospace.com/article/releases/new-analyses-evaluate-long-term-convulsive-seizure-freedom-rates-with-use-of-adjunctive-fycompa-perampanel-ciii-in-adult-patients-presented-at-annual-meeting-of-the-american-epilepsy-society-aes-/

Perampanel (Professional Patient Advice) - Drugs.comPerampanel (Professional Patient Advice) - Drugs.com

95% to 96%; primarily albumin and alpha1-acid glycoprotein. Special Populations: Renal Function Impairment. Apparent clearance ... it is a noncompetitive antagonist of the ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate ... Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy ... Recommended maintenance dose: 8 to 12 mg once daily at bedtime; some patients may respond to 4 mg once daily; 12 mg once daily ...
more infohttps://www.drugs.com/ppa/perampanel.html
  • After their initial expression, the MAP1A and MAP1B polypeptides are cleaved into light and heavy chains, which are then assembled into mature complexes together with the separately encoded light chain 3 subunit (LC3). (biomedcentral.com)
  • Subgroup 3 includes piracetam derivatives with unknown clinical efficacies, and of these nefiracetam failed to improve cognition in post-stroke patients and rolipram is currently in clinical trials as an antidepressant. (springer.com)
  • Furthermore, the activity of MAP1A and MAP1B is controlled by upstream signaling mechanisms, including the MAP kinase and glycogen synthase kinase-3 β pathways. (biomedcentral.com)
  • WOODCLIFF LAKE, N.J. , Dec. 4, 2018 /PRNewswire/ -- Eisai Inc. presented new data on FYCOMPA ® (perampanel) CIII at the American Epilepsy Society Annual Meeting in New Orleans which included analyses of convulsive seizure freedom rates in adult and pediatric epilepsy patients. (biospace.com)
  • In September 2018 , FYCOMPA was approved for monotherapy and adjunctive use in pediatric patients 4 years and older for the treatment of POS with or without secondarily generalized seizures. (biospace.com)
  • 2018 Jan 24;38(4):887-900. (nih.gov)
  • In two- as well as six-transmembrane K + channels, the amino- and carboxy-termini are located intracellularly and are required for tetramerization ( Deutsch, 2002 ). (jneurosci.org)
  • Of note, Eisai presented three post-hoc analyses evaluating the potential of FYCOMPA to help patients experience long-term, sustained convulsive seizure freedom, as well as data that supported the recent U.S. Food and Drug Administration (FDA) approval of FYCOMPA for monotherapy and adjunctive use in pediatric patients 4 years and older for the treatment of partial-onset seizures (POS) with or without secondarily generalized seizures. (biospace.com)
  • These long-term seizure freedom data showed about 53% of patients with secondarily generalized seizures experienced convulsive seizure freedom at 2 years and close to 35% at 3 years," said Trevor Resnick , MD, Pediatric Neurologist at Nicklaus Children's Hospital. (biospace.com)
  • The extracellularly located amino-terminal domain (ATD) mediates dimerization in a subfamily-specific manner ( Mayer, 2011 ). (jneurosci.org)
  • Despite similar sequences to the Q/R site of GluR-B, editing this site does not occur in GluR-3 pre-mRNA. (wikipedia.org)