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.Receptors, Glycine: Cell surface receptors that bind GLYCINE with high affinity and trigger intracellular changes which influence the behavior of cells. Glycine receptors in the CENTRAL NERVOUS SYSTEM have an intrinsic chloride channel and are usually inhibitory.Glycine Agents: Substances used for their pharmacological actions on glycinergic systems. Glycinergic agents include agonists, antagonists, degradation or uptake inhibitors, depleters, precursors, and modulators of receptor function.Glycine Plasma Membrane Transport Proteins: A family of sodium chloride-dependent neurotransmitter symporters that transport the amino acid GLYCINE. They differ from GLYCINE RECEPTORS, which signal cellular responses to GLYCINE. They are located primarily on the PLASMA MEMBRANE of NEURONS; GLIAL CELLS; EPITHELIAL CELLS; and RED BLOOD CELLS where they remove inhibitory neurotransmitter glycine from the EXTRACELLULAR SPACE.Glycine Dehydrogenase (Decarboxylating): A PYRIDOXAL PHOSPHATE dependent enzyme that catalyzes the decarboxylation of GLYCINE with the transfer of an aminomethyl group to the LIPOIC ACID moiety of the GLYCINE DECARBOXYLASE COMPLEX H-PROTEIN. Defects in P-protein are the cause of non-ketotic hyperglycinemia. It is one of four subunits of the glycine decarboxylase complex.Strychnine: An alkaloid found in the seeds of STRYCHNOS NUX-VOMICA. It is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of nonketotic hyperglycinemia and sleep apnea, and as a rat poison.Glycine N-Methyltransferase: An enzyme that catalyzes the METHYLATION of GLYCINE using S-ADENOSYLMETHIONINE to form SARCOSINE with the concomitant production of S-ADENOSYLHOMOCYSTEINE.Glycine Decarboxylase Complex H-Protein: A LIPOIC ACID-containing protein that plays the pivotal role in the transfer of methylamine groups and reducing equivalents between the three enzymatic components of the glycine decarboxylase complex.Betaine: A naturally occurring compound that has been of interest for its role in osmoregulation. As a drug, betaine hydrochloride has been used as a source of hydrochloric acid in the treatment of hypochlorhydria. Betaine has also been used in the treatment of liver disorders, for hyperkalemia, for homocystinuria, and for gastrointestinal disturbances. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1341)Glycine Decarboxylase Complex: A enzyme complex that catalyzes the oxidative DECARBOXYLATION and DEAMINATION of GLYCINE into CARBON DIOXIDE; AMMONIA; NADH; and N5N10-methylenetetrahydrofolate. It is composed of four different component protein components referred to as H, P, L, and T.School Nursing: A nursing specialty concerned with health and nursing care given to primary and secondary school students by a registered nurse.Altretamine: A hexamethyl-2,4,6-triamine derivative of 1,3,5-triazine.Sarcosine: An amino acid intermediate in the metabolism of choline.Amino Acid Transport Systems, Neutral: Amino acid transporter systems capable of transporting neutral amino acids (AMINO ACIDS, NEUTRAL).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.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.Taurine: A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile 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.Aminomethyltransferase: A one-carbon group transferase that transfers lipoamide-linked methylamine groups to tetrahydrofolate (TETRAHYDROFOLATES) to form methylenetetrahydrofolate and AMMONIA. It is one of four components of the glycine decarboxylase complex.Amino Acid Oxidoreductases: A class of enzymes that catalyze oxidation-reduction reactions of amino acids.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.Kynurenic Acid: A broad-spectrum excitatory amino acid antagonist used as a research tool.Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.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.Kinetics: The rate dynamics in chemical or physical systems.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.Glycine Dehydrogenase: An oxidoreductase that catalyzes the oxidative DEAMINATION of GLYCINE to glyoxylate and AMMONIA in the presence of NAD. In BACTERIA lacking transaminating pathways the enzyme can act in the reverse direction to synthesize glycine from glyoxylate and ammonia and NADH.Amidinotransferases: Enzymes of a subclass of TRANSFERASES that catalyze the transfer of an amidino group from donor to acceptor. EC 2.1.4.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.Proline: A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.RNA, Transfer, Gly: A transfer RNA which is specific for carrying glycine to sites on the ribosomes in preparation for protein synthesis.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Hippurates: Salts and esters of hippuric acid.Tiopronin: Sulfhydryl acylated derivative of GLYCINE.Aluminum Compounds: Inorganic compounds that contain aluminum as an integral part of the molecule.Ocotea: A plant genus in the LAURACEAE family. The common name of stinkwood is also used for Zieria (RUTACEAE).Glycine Transaminase: A PYRIDOXAL PHOSPHATE containing enzyme that catalyzes the transfer of the amino group of GLYCINE onto 2-oxoglutarate to generate GLYOXYLATE and L-GLUTAMATE.Aminobutyrates: Derivatives of BUTYRIC ACID that contain one or more amino groups attached to the aliphatic structure. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the aminobutryrate structure.Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.beta-Alanine: An amino acid formed in vivo by the degradation of dihydrouracil and carnosine. Since neuronal uptake and neuronal receptor sensitivity to beta-alanine have been demonstrated, the compound may be a false transmitter replacing GAMMA-AMINOBUTYRIC ACID. A rare genetic disorder, hyper-beta-alaninemia, has been reported.Receptors, GABA: Cell-surface proteins that bind GAMMA-AMINOBUTYRIC ACID with high affinity and trigger changes that influence the behavior of cells. GABA-A receptors control chloride channels formed by the receptor complex itself. They are blocked by bicuculline and usually have modulatory sites sensitive to benzodiazepines and barbiturates. GABA-B receptors act through G-proteins on several effector systems, are insensitive to bicuculline, and have a high affinity for L-baclofen.Betaine-Aldehyde Dehydrogenase: An NAD+ dependent enzyme that catalyzes the oxidation of betain aldehyde to BETAINE.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.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.Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to GLYCINE in the liver and excreted as hippuric acid.Hydroxymethyl and Formyl Transferases: Enzymes that catalyze the transfer of hydroxymethyl or formyl groups. EC 2.1.2.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.N-Methylaspartate: An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Alteromonadaceae: A family of marine, gram-negative PROTEOBACTERIA including the genera ALTEROMONAS; Colwellia; Idiomarina; MARINOBACTER; MORITELLA; PSEUDOALTEROMONAS; and SHEWANELLA.Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.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.Bicuculline: An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.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.Choline Dehydrogenase: An enzyme bound to the inner mitochondrial membrane that catalyzes the oxidation of CHOLINE to BETAINE.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.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.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.Osteogenesis Imperfecta: COLLAGEN DISEASES characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. Most types are autosomal dominant and are associated with mutations in COLLAGEN TYPE I.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.Osmotic Pressure: The pressure required to prevent the passage of solvent through a semipermeable membrane that separates a pure solvent from a solution of the solvent and solute or that separates different concentrations of a solution. It is proportional to the osmolality of the solution.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).Oocytes: Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).Neural Inhibition: The function of opposing or restraining the excitation of neurons or their target excitable cells.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Carbon Isotopes: Stable carbon atoms that have the same atomic number as the element carbon, but differ in atomic weight. C-13 is a stable carbon isotope.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.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.Water-Electrolyte Balance: The balance of fluid in the BODY FLUID COMPARTMENTS; total BODY WATER; BLOOD VOLUME; EXTRACELLULAR SPACE; INTRACELLULAR SPACE, maintained by processes in the body that regulate the intake and excretion of WATER and ELECTROLYTES, particularly SODIUM and POTASSIUM.

Hsp60 is targeted to a cryptic mitochondrion-derived organelle ("crypton") in the microaerophilic protozoan parasite Entamoeba histolytica. (1/5843)

Entamoeba histolytica is a microaerophilic protozoan parasite in which neither mitochondria nor mitochondrion-derived organelles have been previously observed. Recently, a segment of an E. histolytica gene was identified that encoded a protein similar to the mitochondrial 60-kDa heat shock protein (Hsp60 or chaperonin 60), which refolds nuclear-encoded proteins after passage through organellar membranes. The possible function and localization of the amebic Hsp60 were explored here. Like Hsp60 of mitochondria, amebic Hsp60 RNA and protein were both strongly induced by incubating parasites at 42 degreesC. 5' and 3' rapid amplifications of cDNA ends were used to obtain the entire E. histolytica hsp60 coding region, which predicted a 536-amino-acid Hsp60. The E. histolytica hsp60 gene protected from heat shock Escherichia coli groEL mutants, demonstrating the chaperonin function of the amebic Hsp60. The E. histolytica Hsp60, which lacked characteristic carboxy-terminal Gly-Met repeats, had a 21-amino-acid amino-terminal, organelle-targeting presequence that was cleaved in vivo. This presequence was necessary to target Hsp60 to one (and occasionally two or three) short, cylindrical organelle(s). In contrast, amebic alcohol dehydrogenase 1 and ferredoxin, which are bacteria-like enzymes, were diffusely distributed throughout the cytosol. We suggest that the Hsp60-associated, mitochondrion-derived organelle identified here be named "crypton," as its structure was previously hidden and its function is still cryptic.  (+info)

Carbon 13 NMR study of nonenzymatic reactions of pyridoxal 5'-phosphate with selected amino acids and of related reactions. (2/5843)

Carbon 13 nuclear magnetic resonance spectroscopy has been used to monitor the nonenzymatic reactions of pyridoxal 5'-phosphate with glycine, alanine, valine, serine, and with several other model compounds. Isotopically enriched amino acids were employed so that low concentrations could be utilized while still allowing relatively rapid acquisition of spectral data. The results for alanine and serine are particularly noteworthy in that alanine is deaminated to pyruvate and pyruvate is aminated to alanine, but contrary to the enzymatic reactions of various serine dehydratases wherein serine is converted to pyruvate, the nonenzymatic reaction utilizing serine results in hydroxypruvate rather than pyruvate formation. In the reverse reaction, hydroxypyruvate is aminated to serine but very inefficiently relative to the amination of pyruvate to alanine. The experimental results have been formulated into a proposed reaction mechanism for deamination of amino acids by pyridoxal-P.  (+info)

Presence of the vesicular inhibitory amino acid transporter in GABAergic and glycinergic synaptic terminal boutons. (3/5843)

The characterization of the Caenorhabditis elegans unc-47 gene recently allowed the identification of a mammalian (gamma)-amino butyric acid (GABA) transporter, presumed to be located in the synaptic vesicle membrane. In situ hybridization data in rat brain suggested that it might also take up glycine and thus represent a general Vesicular Inhibitory Amino Acid Transporter (VIAAT). In the present study, we have investigated the localization of VIAAT in neurons by using a polyclonal antibody raised against the hydrophilic N-terminal domain of the protein. Light microscopy and immunocytochemistry in primary cultures or tissue sections of the rat spinal cord revealed that VIAAT was localized in a subset (63-65%) of synaptophysin-immunoreactive terminal boutons; among the VIAAT-positive terminals around motoneuronal somata, 32.9% of them were also immunoreactive for GAD65, a marker of GABAergic presynaptic endings. Labelling was also found apposed to clusters positive for the glycine receptor or for its associated protein gephyrin. At the ultrastructural level, VIAAT immunoreactivity was restricted to presynaptic boutons exhibiting classical inhibitory features and, within the boutons, concentrated over synaptic vesicle clusters. Pre-embedding detection of VIAAT followed by post-embedding detection of GABA or glycine on serial sections of the spinal cord or cerebellar cortex indicated that VIAAT was present in glycine-, GABA- or GABA- and glycine-containing boutons. Taken together, these data further support the view of a common vesicular transporter for these two inhibitory transmitters, which would be responsible for their costorage in the same synaptic vesicle and subsequent corelease at mixed GABA-and-glycine synapses.  (+info)

Multiplex sequence analysis demonstrates the competitive growth advantage of the A-to-G mutants of clarithromycin-resistant Helicobacter pylori. (4/5843)

Clarithromycin resistance in Helicobacter pylori is due to point mutation within the 23S rRNA. We examined the growth rates of different types of site-directed mutants and demonstrated quantitatively the competitive growth advantage of A-to-G mutants over other types of mutants by a multiplex sequencing assay. The results provide a rational explanation of why A-to-G mutants are predominantly observed among clarithromycin-resistant clinical isolates.  (+info)

The role of proline and glycine in determining the backbone flexibility of a channel-forming peptide. (5/5843)

Alamethicin is a helical 20-amino acid voltage-gated channel-forming peptide, which is known to exhibit segmental flexibility in solution along its backbone near alpha-methylalanine (MeA)-10 and Gly-11. In an alpha-helical configuration, MeA at position 10 would normally hydrogen-bond with position 14, but the presence of proline at this position prevents the formation of this interhelical hydrogen bond. To determine whether the presence of proline at position 14 contributes to the flexibility of this helix, two analogs of alamethicin were synthesized, one with proline 14 replaced by alanine and another with both proline 14 and glycine 11 replaced by alanine. The C-termini of these peptides were derivatized with a proxyl nitroxide, and paramagnetic enhancements produced by the nitroxide on the Calpha protons were used to estimate r-6 weighted distances between the nitroxide and the backbone protons. When compared to native alamethicin, the analog lacking proline 14 exhibited similar C-terminal to Calpha proton distances, indicating that substitution of proline alone does not alter the flexibility of this helix; however, the subsequent removal of glycine 11 resulted in a significant increase in the averaged distances between the C- and N-termini. Thus, the G-X-X-P motif found in alamethicin appears to be largely responsible for mediating high-amplitude bending motions that have been observed in the central helical domain of alamethicin in methanol. To determine whether these substitutions alter the channel behavior of alamethicin, the macroscopic and single-channel currents produced by these analogs were compared. Although the substitution of the G-X-X-P motif produces channels with altered characteristics, this motif is not essential to achieve voltage-dependent gating or alamethicin-like behavior.  (+info)

NMDA receptor characterization and subunit expression in rat cultured mesencephalic neurones. (6/5843)

1. NMDA-induced changes in free intracellular Ca2+ concentration ([Ca2+]i) were determined in individual cultured rat mesencephalic neurones by the fura-2 method. mRNA expression encoding NMDA receptor subunits (NR1, NR2A-D) was examined by RT-PCR. 2. NMDA (1-100 microM, plus 10 microM glycine) induced a concentration-dependent increase in [Ca2+]i (EC50 = 5.7 microM). The effect of NMDA was virtually insensitive to tetrodotoxin (0.3 microM) and nitrendipine (1 microM), but dependent on extracellular Ca2+. 5,7-Dichlorokynurenic acid (10 microM), a specific antagonist at the glycine binding site on the NMDA receptor, abolished the NMDA response. 3. Memantine, an open-channel blocker, and ifenprodil, a preferential non-competitive NR1/NR2B receptor antagonist diminished the NMDA effect with an IC50 value of 0.17 and 1 microM, respectively. Ethanol at 50 and 100 mM caused about 25 and 45%-inhibition, respectively. 4. Agarose gel analysis of the PCR products followed by ethidium bromide fluorescence or CSPD chemiluminescence detection revealed an almost exclusive expression of the NR1 splice variants lacking exon (E) 5 and E22. The 3' splice form without both E21 and E22 exceeded that containing E21 by approximately 4 fold. The relative amounts of NR2A, NR2B, NR2C corresponded to approximately 1:2:1. NR2D mRNA was also detectable. 5. In conclusion, mesencephalic neurones bear ethanol-sensitive NMDA receptors which might be involved in the development of ethanol dependence and withdrawal. The high affinity of NMDA to this receptor, its sensitivity to ifenprodil and memantine may suggest that the mesencephalic NMDA receptor comprises the NR1 splice variant lacking E5, NR2B, and NR2C, respectively.  (+info)

Antagonist activity of alpha-substituted 4-carboxyphenylglycine analogues at group I metabotropic glutamate receptors expressed in CHO cells. (7/5843)

1. We have investigated the antagonist properties of 6 alpha-substituted phenylglycine analogues based on the structure of 4-carboxyphenylglycine (4-CPG) for group I metabotropic glutamate receptors (mGlu1alpha and mGlu5a) permanently expressed in CHO cells. 2. (S)-4-CPG and (S)-MCPG were the most selective mGlu1alpha receptor antagonists. Longer chain alpha-carbon substitutions resulted in a progressive loss of antagonist affinity at mGlu1alpha receptors but not at mGlu5a receptors. Thus mGlu1alpha receptor antagonists require small aliphatic groups at the alpha-position. Alpha-cyclopropyl-4-CPG showed a tendency towards mGlu5a selectivity, suggesting that bulky groups at this position may favour mGlu5a receptor antagonism. 3. We demonstrate that the mGlu5a receptor displays agonist-dependent antagonism. L-glutamate-induced Ca2+ release in mGlu5a receptor expressing cells was more susceptible to antagonism by cyclic alpha-carbon derivatives than (S)-3,5-dihydroxyphenylglycine (DHPG)-induced Ca2+ release in the same cell line. 4. The data presented suggests that mGlu1alpha and mGlu5a receptors have different steric and/or conformational requirements for the binding of antagonists and different amino acids which could interact with agonists. 5. These phenylglycine analogues could provide leads for the development of subtype selective antagonists.  (+info)

Mechanisms involved in the metabotropic glutamate receptor-enhancement of NMDA-mediated motoneurone responses in frog spinal cord. (8/5843)

1. The metabotropic glutamate receptor (mGluR) agonist trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD) (10-100 microM) depolarized isolated frog spinal cord motoneurones, a process sensitive to kynurenate (1.0 mM) and tetrodotoxin (TTX) (0.783 microM). 2. In the presence of NMDA open channel blockers [Mg2+; (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK801); 3,5-dimethyl-1-adamantanamine hydrochloride (memantine)] and TTX, trans-ACPD significantly potentiated NMDA-induced motoneurone depolarizations, but not alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA)- or kainate-induced depolarizations. 3. NMDA potentiation was blocked by (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) (240 microM), but not by alpha-methyl-(2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine (MCCG) (290 microM) or by alpha-methyl-(S)-2-amino-4-phosphonobutyrate (L-MAP4) (250 microM), and was mimicked by 3,5-dihydroxyphenylglycine (DHPG) (30 microM), but not by L(+)-2-amino-4-phosphonobutyrate (L-AP4) (100 microM). Therefore, trans-ACPD's facilitatory effects appear to involve group I mGluRs. 4. Potentiation was prevented by the G-protein decoupling agent pertussis toxin (3-6 ng ml(-1), 36 h preincubation). The protein kinase C inhibitors staurosporine (2.0 microM) and N-(2-aminoethyl)-5-isoquinolinesulphonamide HCI (H9) (77 microM) did not significantly reduce enhanced NMDA responses. Protein kinase C activation with phorbol-12-myristate 13-acetate (5.0 microM) had no effect. 5. Intracellular Ca2+ depletion with thapsigargin (0.1 microM) (which inhibits Ca2+/ATPase), 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetracetic acid acetyl methyl ester (BAPTA-AM) (50 microM) (which buffers elevations of [Ca2+]i), and bathing spinal cords in nominally Ca2+-free medium all reduced trans-ACPD's effects. 6. The calmodulin antagonists N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W7) (100 microM) and chlorpromazine (100 microM) diminished the potentiation. 7. In summary, group I mGluRs selectively facilitate NMDA-depolarization of frog motoneurones via a G-protein, a rise in [Ca2+]i from the presumed generation of phosphoinositides, binding of Ca2+ to calmodulin, and lessening of the Mg2+-produced channel block of the NMDA receptor.  (+info)

  • Data obtained from whole-cell patch-clamp recordings of hippocampal pyramidal neurons, in vitro , demonstrated that exogenous glycine and glycine transporter type 1 (GLYT1) antagonist selectively enhanced the amplitude of the NMDA component of a glutamatergic excitatory postsynaptic current. (
  • Of these, the glycine transporter type 1 (GLYT1) is expressed primarily in glia and neurons of the neocortex and archicortex in association with regions of high NMDA expression ( 15 - 17 ). (
  • The recent discovery of glycine transporters in both the central nervous system and the periphery suggests that glycine transport may be critical to N -methyl- d -aspartate receptor (NMDAR) function by controlling glycine concentration at the NMDAR modulatory glycine site. (
  • Even though glycine is a non-essential amino acid, which means it may be synthesized from in the human body, it is nevertheless important in many metabolic pathways. (
  • Glycine is also used for treatment of various diseases such as stroke, schizophrenia, some rare metabolic disorders. (
  • We examined the role of glycine and GLYT1 on synaptic currents elicited by stimulation of the CA3-CA1 Schaffer collateral axons in hippocampal slices of the rat in vitro . (
  • Manufacturers advertising glycine supplements have made a number of additional claims for it, including prevention of epileptic seizures , reducing acid in the stomach, multiple sclerosis , boosting the immune system , and calming the mind. (
  • After bringing together a list of supplements to buy for my next stack, I came across Glycine. (
  • By combining carbohydrates and glycine there has been shown to be a greater use of glucose for energy before, during and after exercise resulting in improved lean growth and recovery. (
  • This is thought to be due to greater glucose uptake due to an increase in insulin sensitivity when combined with Glycine. (
  • Furthermore, GLYT1 antagonist enhanced NMDAR function during perfusion with medium containing 10 μM glycine, a concentration similar to that in the cerebrospinal fluid in vivo , thereby supporting the hypothesis that the GLYT1 maintains subsaturating concentration of glycine at synaptically activated NMDAR. (
  • Glycine is also an inhibitory neurotransmitter in the central nervous system and has been shown to help improve sleep quality when taken before bedtime so is useful for those who struggle to get a good quality of sleep throughout the night. (
  • however, the effective concentration of the applied glycine could not be determined and its physiological role in NMDAR modulation remains unclear ( 9 ). (
  • This is in large part because the concentration of glycine in the cerebrospinal fluid is about 6 μM ( 10 ), which ought to saturate the NMDAR glycine site. (
  • A small double-blind study found evidence that glycine may help improve long-term blood sugar control in people with type 2 diabetes. (