Search Results - (Author, Cooperation:Michaëlis)

Selter, Christoph [Herausgeber]; Hußmann, Stephan [Herausgeber]; Hößle, Corinna [Herausgeber]; Knipping, Christine [Herausgeber]; Lengnink, Katja [Herausgeber]; Michaelis, Julia [Herausgeber]

Book

279 Seiten :, Illustrationen, Diagramme ;, 24 cm x 17 cm

9783830937401, 978-3-8309-3740-1, 3830937407

German

Michaelis, H.; Müller-Guntrum, H.; Staudte, A.; Treeß, U.

Unknown

229 S.

3. Aufl.

340762056X

Curriculum-Materialien für Vorschule und Eingangsstufe Bd. 2

German

Michaelis, Wolfgang

Unknown

142 S.

German

book

1999

Erziehung ; Pädagogik ; Gender ; Gender Mainstreaming ; Rezeption ; Sozialisation ; Familie ; Fernsehen ; Medien ; Medienerziehung ; Medienpädagogik ; Medienwelt ; Förderung ; Kindertagesstätte ; Schule ; Elternabend ; Elternarbeit ; Elternbildung ; Familienberatung ; Geschlechtsspezifik ; Handbuch ; Hilfe ; Nachschlagewerk

German

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract: N-Methyl-d-asparate receptors (NMDARs) are a major target of ethanol effects in the nervous system. Haloperidol-insensitive, but dizocilpine (MK-801)-sensitive, binding of N-[1-(2-[3H]thienyl)cyclohexyl]piperidine ([3H]TCP) to synaptic membranes has the characteristics of ligand interaction with the ion channel of NMDARs. In the present studies, ethanol produced a concentration-dependent decrease in the maximal activation of [3H]TCP binding to synaptic membranes by NMDA and Gly, but a moderate change in the activation by l-Glu when l-Glu was present at concentrations 〈 100 µM. However, ethanol (100 mM) inhibited completely the activation of [3H]TCP binding produced by high concentrations of l-Glu (200–400 µM). It also inhibited strongly the activation of [3H]TCP binding by spermidine or spermidine plus Gly. In a purified complex of proteins that has l-Glu-, Gly-, and [3H]TCP-binding sites, ethanol (100 mM) decreased significantly the maximal activation of [3H]TCP binding produced by either l-Glu or Gly. Activation constants (Kact) for l-Glu and Gly acting on the purified complex were 12 and 28 µM, respectively. Ethanol had no significant effect on the Kact of l-Glu but caused an increase in the Kact of Gly. These studies have identified at least one protein complex in neuronal membranes whose response to both l-Glu and Gly is inhibited by ethanol. These findings may explain some of the effects of acute and chronic ethanol treatment on the function and expression of the subunits of this complex in brain neurons.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract: Acute exposure to ethanol inhibits both the NMDA receptors and the Na/Ca-exchange carriers in neuronal membranes. This alters intraneuronal signaling pathways activated by Ca2+. Neurons exposed chronically to ethanol exhibit enhanced density and activity of NMDA receptors and increased maximal activity of the exchangers. In the present study, the expression of brain synaptic membrane proteins with ligand binding sites characteristic of NMDA receptors and of exchange carriers were determined after chronic ethanol administration (15 days) to rats. Such treatment caused an increase in the expression of the NMDAR1 receptor subunit, 15% above the levels in the pair-fed controls, as well as of three subunits of a complex that has properties characteristic of NMDA receptors, the glutamate, carboxypiperazinylphosphonate, and glycine binding proteins. Increases for the three binding proteins were 49, 50, and 62%, respectively. The expression of the 120-kDa exchanger proteins was increased by 14% and that of a 36-kDa exchanger-associated protein by 33%. Both the binding proteins and the exchangers returned to basal levels within 36–72 h after withdrawal from ethanol. No changes were detected in synaptic membrane Ca2+, Mg2+-ATPases. The enhanced expression of receptor and exchanger-associated proteins may explain the increases in the density and activity of NMDA receptors and exchange carriers after chronic ethanol treatment.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

A glutamate-binding protein from rat brain synaptic plasma membranes has been purified to apparent homogeneity. This protein has a Mr of 14,300 based on amino acid and carbohydrate analyses. The protein is enriched with tryptophan residues, which contribute substantially to its hydrophobic nature. It also has a relatively high content of acidic amino acids, which determine its low isoelectric point (4.82). The protein exhibits either a single, high-affinity class of sites for L-[3H]glutamate binding (KD= 0.13 μM) when binding is measured at low protein concentrations, or two classes of sites with high (KD= 0.17 μM) and low affinities (KD= 0.8 μM) when binding is measured at high protein concentrations. These observations suggest preferential binding of L-glutamate to a self-associating form of the protein. The displacement of protein-bound L-[3H]glutamic acid by other neuroac-tive amino acids has characteristics similar to those observed for displacement of L-glutamate from membrane binding sites. Chemical modification of the cysteine and arginine residues results in an inhibition of glutamate binding activity. The possible function of this protein in the physiologic glutamate receptor complex of neuronal membranes is discussed.

Electronic Resource

1749-6632

Blackwell Publishing Journal Backfiles 1879-2005

Natural Sciences in General

Electronic Resource

0005-2736

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Biology

Chemistry and Pharmacology

Medicine

Physics

Electronic Resource

0005-2736

(Rat brain) ; Adenosine analog ; K^+ flux ; Lipophilic action ; Membrane potentials ; Neuronal membrane

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Biology

Chemistry and Pharmacology

Medicine

Physics

Electronic Resource

0014-5793

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Biology

Chemistry and Pharmacology

Physics

Electronic Resource

1432-1440

Springer Online Journal Archives 1860-2000

Medicine

Electronic Resource

1432-1440

Springer Online Journal Archives 1860-2000

Medicine

Electronic Resource

1432-1440

Springer Online Journal Archives 1860-2000

Medicine

Electronic Resource

1432-1440

Springer Online Journal Archives 1860-2000

Medicine

Electronic Resource

1573-4919

Springer Online Journal Archives 1860-2000

Biology

Chemistry and Pharmacology

Medicine

Summary The strong excitatory activity of L-glutamic acid on central nervous system neurons is thought to be produced by interaction of this amino acid with specific neuronal plasma membrane receptors. The binding of L-glutamate to these surface receptors brings about an increase in membrane permeability to Na+ and Ca2+ ions presumably through direct activation of ion channels linked to the membrane receptors. The studies described in this paper represent attempts to define the subcellular distribution and pharmacological properties of the recognition site for L-glutamic acid in brain neuronal preparations, to isolate and explore the molecular characteristics of the receptor recognition site, and, finally, to demonstrate the activation of Na+ channels in synaptic membranes following the interaction of glutamate with its receptors. Radioligand binding assays with L-[3H] glutamic acid have been used to demonstrate a relative enrichment of these glutamate recognition sites in isolated synaptic plasma membranes. The specific binding of L-[3H] glutamate to these membrane sites exhibits rapid association and dissociation kinetics and rather complex equilibrium binding kinetics. The glutamate binding macromolecule from synaptic membranes has been solubilized and purified and was shown to be a small molecular weight glycoprotein (MT ≈ 13 000). This protein tends to form aggregates which have higher specific activity at low concentrations of glutamate than the MT 13 000 protein has. The overall affinity of the purified protein is lower than that of the high affinity sites in the membrane. Nevertheless, the purified protein exhibits pharmacological characteristics very similar to those of the membrane binding sites. On the basis of its pharmacological properties this protein belongs in the category of the physiologic ‘glutamate preferring’ receptors. By means of differential solubilization of membrane proteins with Na-cholate, it was shown that this recognition site is an intrinsic synaptic membrane protein whose binding activity is enhanced rather than diminished by cholate extraction of the synaptic membranes. The role of membrane constituents in regulating the binding activity of this protein has been explored and a possible modulation of glutamate binding by membrane gangliosides has been demonstrated. Finally, this glutamate binding glycoprotein is a metalloprotein whose activity is dependent on the integrity of its metallic (Fe) center. This is a clear distinguishing characteristic of this protein vis-à-vis the glutamate transport carriers. The presence of functional glutamate receptors in synaptosomes and resealed synaptic plasma membranes has also been documented by the demonstration of glutamate-activated Na+ flux across the membrane of these preparations. The bidirectionality, temperature independence, and apparent desensitization of this stimulated flux following exposure to high concentrations of glutamate are properties indicative of a receptor-initiated ion channel activation. It would appear, then, that the synaptic membrane preparations provide a very useful system for the study of both recognition and effector function of the glutamate receptor complex.

Electronic Resource

1432-2048

Springer Online Journal Archives 1860-2000

Biology

Electronic Resource

1573-6903

NMDA receptors ; intracellular Ca2+ ; NMDAR1 ; glutamate-binding protein ; nitric oxide synthase ; neurotoxicity ; receptor expression

Springer Online Journal Archives 1860-2000

Medicine

Abstract Cerebellar granule cells maintained in vitro as primary cultures are a relatively homogeneous neuronal population that can be used to evaluate the developmental expression of neurotransmitter receptors and to assess their role in cell survival and degeneration. The toxicity induced by N-methyl-d-aspartate (NMDA) in granule cells maintained under partially depolarizing conditions and in the presence of physiologic extracellular concentrations of Mg2+ was greatest for the neurons maintained for 14 days in vitro (DIV). However, following NMDA receptor activation neurons as young as 5 DIV exhibited increases in the concentration of intracellular free Ca2+ which were as large as those achieved with cells at 8–9 or 13–14 DIV. The less mature neurons exhibited a “down-regulation” of responses to increasing concentrations of NMDA and the more mature cells maintained elevated intracellular Ca2+ levels during the inter-stimulus periods. Immunochemical analyses of the expression of the NMDA receptor-associated proteins NMDAR1 and glutamatebinding protein (GBP) in granule cells indicated a developmental increase in both proteins, albeit the pattern of expression of NMDAR1 was the more complex. No definite correlation has yet been established between toxicity induced by NMDA and the expression of these two proteins. Finally, although the developmental expression of nitric oxide synthase, an enzyme that catalyzes the formation of the potentially neurotoxic radicals nitric oxide and superoxide anion, increased progressively with the maturation of neurons in culture, an inhibitor of this enzyme did not protect neurons from NMDA-induced toxicity. Therefore, the developmental changes in granule cells that lead to increased vulnerability following excessive activation of NMDA receptors are not yet completely defined.

Electronic Resource

1573-6903

NMDA receptors ; synaptic membranes ; calcium ; sodium

Springer Online Journal Archives 1860-2000

Medicine

Abstract N-Methyl-d-aspartate (NMDA) andl-glutamate activate membrane receptor that produce substantial permeation of Na+, K+ and Ca2+ through the neuronal membrane. These ionic fluxes are intimately linked to processes that regulate neuronal survival, growth and differentiation. Intracellular free Ca2+ concentrations are thought to be particularly important determinants of the vulnerability of neurons to excessive excitatory stimulation produced through activation of NMDA receptors. In order to understand the molecular events involved in both NMDA receptor activation and regulation of intracellular Ca2+ levels, we have purified and reconstituted the protein complexes that form the NMDA/glutamate receptors in rat brain synaptic membranes and those that constitute the Na+-Ca2+ antiporters in bovine brain synaptic membranes. The molecular properties of these protein complexes are described, and information from the most recent studies of exploration of the molecular structures of these receptors and transport carriers is summarized.

Electronic Resource

1573-6903

Springer Online Journal Archives 1860-2000

Medicine

Abstract Four amphipathic molecules with known local anesthetic activity, dibucaine, tetracaine, chlorpomazine, and quinacrine, inhibited the binding ofl-[3H]glutamic acid to rat brain synaptic plasma membranes and to the purified glutamate binding protein. Neither haloperidol nor diphenylhydantoin had significant inhibitory effects on the glutamate binding activity of the membranes or of the purified protein. The amphipathic drugs apparently inhibitedl-[3H]glutamate binding to synaptic membranes by a mixed type of inhibition. The inhibitory activity of quinacrine on glutamate binding to the synaptic membranes was greater in a low ionic strength, Ca2+-free buffer medium, than in a physiologic medium (Krebs-Henseleit buffer). Removal of Ca2+ from the Krebs solution enhanced quinacrine's inhibition of glutamate binding. Quinacrine up to 1 mM concentration did not inhibit the high affinity Na+-dependentl-glutamate transport in these membrane preparations. The importance of Ca2+ in the expression of quinacrine's effects on the glutamate binding activity of synaptic membranes and the observed tetracaine and chlorpromazine-induced increases in the transition temperature for the glutamate binding process of these membranes, were indicative of an interaction of the local anesthetics with the lipid environment of the glutamate binding sites.

Electronic Resource