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  • 1
    Online Resource
    Online Resource
    Berlin, Heidelberg :Springer Berlin / Heidelberg,
    Keywords: Electronic books.
    Description / Table of Contents: Proceedings of the NATO Advanced Research Workshop on Nicotine Acetylcholine Receptors in the Nervous System held in Venice, Italy, April 18-21, 1988.
    Type of Medium: Online Resource
    Pages: 1 online resource (432 pages)
    Edition: 1st ed.
    ISBN: 9783642741678
    Series Statement: Nato asi Subseries H: Series ; v.25
    Language: English
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effects of the acetylcholinesterase inhibitors physostigmine and tacrine on α4β2 and α4β4 subtypes of neuronal nicotinic acetylcholine (ACh) receptors, expressed in Xenopus laevis oocytes, have been investigated. In voltage-clamp experiments low concentrations of physostigmine and tacrine potentiate ion currents induced by low concentrations of ACh, whereas at high concentrations they inhibit ACh-induced ion currents. These dual effects result in bell-shaped concentration—effect curves. Physostigmine and tacrine, by themselves, do not act as nicotinic receptor againsts. The larger potentiation is observed with 10 μM physostigmine on α4β4 nicotinic receptors and amounts to 70% at 1 μM ACh. The mechanism underlying the effects of physostigmine on α4β4 ACh receptors has been investigated in detail. Potentiation of ACh-induced ion current by low concentrations of physostigmine is surmounted at elevated concentrations of ACh, indicating that this is a competitive effect. Conversely, inhibition of ACh-induced ion current by high concentrations of physostigmine is not surmounted at high concentrations of ACh, and this effect appears mainly due to noncompetitive, voltage-dependent ion channel block. Radioligand binding experiments demonstrating displacement of the nicotinic receptor agonist 125I-epibatidine from its recognition sites on α4β4 ACh receptors by physostigmine confirm that physostigmine is a competitive ligand at these receptors. A two-site equilibrium receptor occupation model, combined with noncompetitive ion channel block, accounts for the dual effects of physostigmine and tacrine on ACh-induced ion currents. It is concluded that these acetylcholinesterase-inhibiting drugs interact with the ACh recognition sites and are coagonists of ACh on α4-containing nicotinic ACh receptors.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The expression of neurotransmitter receptors on the surface of immunocompetent cells is generally accepted as evidence that the nervous system can influence immune responses, even though many aspects of these interactions remain to be elucidated. In this article, we analyzed the expression of the α3 nicotinic receptor subunit in human cell lines of myeloid and lymphoid origin and show that the α3 mRNA and the receptor molecules containing this subunit are specifically expressed in T lymphocyte cell lines. We have previously characterized the structural properties of the human α3 nicotinic subunit gene promoter and defined its functional profile in neuronal cells; in this study, we analyzed the activity of the α3 promoter in T lymphocytes and found that the same minimal promoter located in the 0.16-kb BglII-AccIII fragment is responsible for the expression of the α3 mRNA in both neuronal and T lymphocyte cell lines. However, the α3 transcription initiation patterns in the two cell types were both qualitatively and quantitatively different, and the minimal promoter was differentially modulated by downstream and upstream regulatory elements. These findings suggest that distinct transcriptional mechanisms allow the same promoter to be regulated in a tissue-specific fashion, according to the different functional needs of the two cell types.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Biochemistry 21 (1982), S. 3148-3154 
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Nicotinic receptors are present in the chick retina, but their structure and functional characteristics are still unclear. Using anti-α7 and anti-α8 subunit-specific antibodies, we immunopurified the α7 and α8 subtypes of chick retina neuronal nicotinic receptors. When analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, the two purified subtypes consistently showed a similar peptide composition characterized by the presence of two major peptides of Mr 58 ± 1 and 54 ± 1 kDa, and two minor peptides of 67 and 61 ± 1 kDa. In the α7 subtype, the 58 kDa peptide was recognized by anti-α7 but not by anti-α8 antibodies; in the α8 subtype, the 58 kDa peptide was recognized only by anti-α8 antibodies. The α7 subtype had a single class of [125]a-bungarotoxin binding sites with a KD value of 1.2 nM, whereas the purified α8 subtype had two classes of binding sites, one with a KD of 5.5 nM and the other with very high affinity (KD 52 pM), but present in only 8% of the receptors. Competition binding experiments also showed the presence on the α8 subtype of highand low-affinity classes of binding sites; the affinity for cholinergic drugs of the former was greater than that of the single class present on the α7 subtype. When reconstituted in planar lipid bilayers, both subtypes formed ligand-gated cation channels with major conductance levels of 42 and 52 pS but with different lifetimes; the two channels were activated by agonists and blocked by d-tubocurarine and the glycinergic antagonist strychnine. In line with the binding data, the reconstituted α8 subtype had greater agonist sensitivity than the α7 subtype.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-6822
    Keywords: aluminum ; cadmium ; cell differentiation ; cholinergic receptors ; human neuroblastoma ; lead ; neurotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Neurotoxicity of long-term exposure to lead, aluminum and cadmium has been studied in vitro on the human neuroblastoma cell line IMR32 by measuring cytotoxicity, and the effects on neuronal-specific characteristics such as nitrite outgrowth and expression of cholinergic receptors as parameters of toxicity. Cytotoxicity was highest with cadmium, intermediate with lead and lowest with aluminum exposure. Lead, but not cadmium and aluminum, interfered with neurite growth. The expression of a-bungarotoxin binding sites and muscarinic receptors was markedly increased by cadmium and not affected by aluminum exposure. Lead induced only an increase of toxin binding sites. These in vitro modifications are discussed in relation to the possible use of neuronal cell lines for detecting neurotoxic effects of heavy metals.
    Type of Medium: Electronic Resource
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