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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: A comparison of the pharmacological and physiological properties of the metabotropic glutamate 1α and 1β receptors (mGluR1α and mGluR1β) expressed in baby hamster kidney (BHK 570) cells was performed. The mGluR1β receptor is an alternatively spliced form of mGluR1α with a modified carboxy terminus. Immunoblots of membranes from the two cell lines probed with receptor-specific antipeptide antibodies showed that mGluRIa migrated with an Mr= 154, 000, whereas mGluR1β migrated with an Mr= 96, 000. Immunofluorescence imaging of receptors expressed in BHK 570 cells revealed that the mGluR1α receptor was localized to patches along the plasmalemma and on intracellular membranes surrounding the nucleus, whereas mGluR1β was distributed diffusely throughout the cell. Agonist activation of the mGluR1α and the mGluR1β receptors stimulated phosphoinositide hydrolysis. At both receptors, glutamate, quisqualate, and ibotenate were full agonists, whereas trans-(+)-1-aminocyclopentane-1, 3-dicarboxylate appeared to act as a partial agonist. The stimulation of phosphoinositide hydrolysis by mGluR1α showed pertussis toxin-sensitive and insensitive components, whereas the mGluR1β response displayed only the toxin-insensitive component. The mGluR1α and mGluR1β receptors also increased intracellular calcium levels by inducing release from intracellular stores. These results indicate that the different carboxy terminal sequences of the two receptors directly influences G protein coupling and subcellular deposition of the receptor polypeptides and suggest that the two receptors may subserve different roles in the nervous system.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Modification of synaptic strength in the mammalian central nervous system (CNS) occurs at both pre- and postsynaptic sites,. However, because postsynaptic receptors are likely to be saturated by released transmitter, an increase in the number of active postsynaptic receptors may be a more ...
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 65 (1987), S. 520-526 
    ISSN: 1432-1106
    Keywords: Intracellular free Ca2+ ; Quin2 ; Brain cells ; Ca2+ channels ; Excitatory amino acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Dispersed brain cells from 12–14 day old mouse embryos were loaded with the Ca2+-sensitive fluorescent probe, quin2 and shown to have a resting intracellular Ca2+ concentration ([Ca2+]i) of 158 nM (SE ± 5) in the presence of 1 mM [Ca2+]o. When external [Ca2+] was raised from 0 to 1 mM there was an increase of [Ca2+]i of 70 nM; with further additions of Ca to 〉10 mM [Ca2+]o the level of [Ca2+]i increased by 〈25 nM. Releasable intracellular Ca2+ stores, estimated from the increase in [Ca2+] produced by 4Br A23187 in the absence of extracellular Ca2+, were 24 fmol/106 cells. A small increase in [Ca2+]i could be produced by the mitochondrial inhibitor, carbonyl cyanide m-chlorophenylhydrazone (CCCP). When extracellular K+ was raised by 10–20 mM, intracellular Ca2+ levels increased from 152 (SE ± 7) to 204 nM (SE ± 10). These K+-induced increases in [Ca2+]i were blocked by verapamil, did not occur in the absence of extracellular Ca2+, and presumably reflect the activation of voltage-dependent Ca2+ channels. N-methyl-D-aspartic acid (NMDA) evoked an increase in [Ca2+]i, while the kainate-like lathyrus sativus neurotoxin, L-3-oxalyl-amino-2aminopropionic acid (L-3,2-OAP) did not; this is consistent with previous observations of different and respectively Ca2+-dependent and -independent mechanisms of action of these excitatory amino acids.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 57 (1984), S. 158-166 
    ISSN: 1432-1106
    Keywords: Lathyrus neurotoxin ; Excitatory amino acids ; Spinal cord neurons ; Intracellular analysis ; Ionic mechanisms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intracellular recordings were made in cultured neurones from foetal mouse spinal cord. The effects of applications of the neurotoxin, L-3-oxalylamino-2-amino-propionic acid (a constituent of the chickling pea, Lathyrus sativus) and its 2-oxalyl-amino isome on membrane potential and conductance were examined in the presence of TTX and TEA and compared to those of other excitatory amino acids. Although both compounds produced membrane depolarization and an increase in input conductance, the 3-oxalylamino isomer (β-ODAP) was ≅ 10 times more potent than the 2-oxalylamino isomer (α-ODAP). β-ODAP caused a voltage-independent change in conductance, as compared to an apparent voltage-dependent decrease produced in the same neurons by L-aspartic acid (L-ASP). Although reversal potentials determined for β-ODAP resembled those for α-ODAP and kainic acid, they were consistently and significantly lower than the reversal level for L-ASP. Although the receptor antagonist 2-amino-5-phosphonovaleric acid (APV) and the divalent cation Cd2+ did not alter the conductance increase evoked by β-ODAP, they markedly depressed responses to L-ASP. Such differences suggest a mechanism of excitatory action for the neurotoxin, β-ODAP, which does not involve a Ca2+-dependent mechanism and is quite different from that for L-ASP and N-methyl-D-aspartic acid, but similar to that of kainic and quisqualic acids. It is proposed that excitatory effects of amino acids (e.g. β-ODAP and kainic acid) which involve a voltage-independent mechanism may somewhat paradoxically promote, by means of persistent depolarization, a greater and more toxic accumulation of intracellular Ca2+ than those with a voltage-dependent mechanism (e.g. L-ASP) which activate large oscillations of membrane potential but perhaps more transient influx of Ca2+.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1106
    Keywords: Retina ; Cytoarchitecture ; Development ; Retinal pigment epithelium ; Mouse ; Cats ; Guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The objective of this study was to investigate the cellular processes involved in the formation of the cytoarchitectonics of the retina. Neurons derived from the retina, spinal cord, cerebral cortex and hippocampus were grown in dissociated monolayer tissue culture using standard techniques. The cultures of retina were unique in that the neurons actively formed into itcell clusters. On the other hand, cultures of neurons from the other regions of the CNS grew without forming any obvious histotypical pattern. Cell clusters consisted of an apparent monolayer of neurons above a population of flat cells and clusters were observed in retinal cultures derived from all species studied (mouse, cat and guinea pig). Each cluster was surrounded by whorls of fibroblasts; astrocytes (GFAP-positive cells) were often closely associated with clusters. Formation of clusters appeared to depend strongly upon the presence of cells derived from the retinal pigment epithelium (RPE) because the ability of retinal cells to form clusters was markedly impaired when the RPE was omitted from the cultures. Interestingly, monolayer cultures of neurons from other regions of the CNS could be induced to form clusters, but only when cells of the RPE layer were included at the time of plating. In cultures grown without the RPE layer, clusters did not form when media taken from cultures expressing clusters was used, indicating that the formation of clusters was not caused by a mediabourne factor. On the other hand, clusters did form when neurons without RPE were grown on feeder plates in which clusters had previously been expressed and the neurons subsequently killed by prolonged culturing or by treatment with kainic acid. Hence, physical contact between neurons and cells derived from the RPE appears critical for the formation of clusters. Our results suggest that the cellular processes underlying the formation of clusters may reflect those in the development of the retina in vivo. Thus, cluster formation may be a useful model for investigating the initial stages in the development of retinal cytoarchitecture.
    Type of Medium: Electronic Resource
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