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  • 1
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Biochemistry 11 (1972), S. 4633-4640 
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 710 (1994), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Muscarinic acetylcholine receptors (mAChRs) play an important role in regulating the release of acetylcholine (ACh) in various tissues. We used subtype-specific antibodies and a fluorescent-labelled muscarinic toxin to demonstrate that mammalian neuromuscular junction expresses mAChR subtypes M1 to M4, and that localization of all subtypes is highly restricted to the innervated part of the muscle. To elucidate the roles of the mAChR subtypes regulating ACh release, we measured the mean quantal content of endplate potentials in isolated mouse phrenic–hemidiaphragm preparations in which release was reduced by a low Ca2+/high Mg2+ medium. Muscarine decreased evoked ACh release in normal junctions but, depending on the concentration, reduced or increased transmitter release in collagen Q-deficient junctions completely lacking acetylcholinesterase (AChE). Both effects were also seen in normal junctions when AChE was inhibited by various doses of fasciculin-2. Block of mAChRs by atropine had no effect on evoked release at normal junctions, but decreased release at junctions lacking AChE. The muscarine-elicited depression of ACh release in normal junctions was completely abolished by pertussis toxin or methoctramine pretreatment, but was not affected by muscarinic toxin MT-3, thus indicating the involvement of the M2 mAChR. The muscarine-induced increase of ACh release in AChE-deficient junctions was not affected by pertussis toxin, but was completely blocked by MT-7, a specific M1 mAChR antagonist. Our results show that the M1 and M2 mAChRs have opposite presynaptic functions in modulating quantal ACh release, and that regulation of release by the two receptor subtypes depends on the functional state of AChE at the neuromuscular junction.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 29 (1973), S. 1319-1327 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Conclusion I have discussed in this article only the most active toxins, with the result that many interesting substances have been omitted, e.g. the toxins from bee and wasp venoms (apamin, melittin, etc.), of many amphibians (bufotoxins, etc.), ciguatoxins, and many more. Poisons are found in every phylum except birds. Shrews exemplify venomous mammals. One gets a good illustration of the number of poisonous animals by studying the monumental and impressive work byHalstead 106 which consequently excludes terrestrial animals. An interesting fact in this connection is that there are about 20,000 species of spiders, most of which are poisonous. A toxin ranking list has to be included in an article of this kind. The list is, of course, far from complete. Data on molecular weights, mouse lethal doses, etc. are lacking for many potent toxins, such as the dysentery toxin, a neurotoxin with a toxicity comparable to that of the botulinus toxins107, the toxins from the jelly fishChironex fleckeri 106. A comparison on molar basis gives a better notion of the toxicities. Curare has about 1/30 of the toxicity of the curarimimetic snake venom neurotoxins, clearly indicating that curare has a much lower affinity for the acetylcholine receptor. Toxic organisms have developed during millions of years more and more refined toxins, and this evolution has probably brought into existence toxins against every physiological function. Neurochemistry is to a great extent unexplored. Progress in this field will in the nearest future depend on specific toxins from various natural sources. Toxins from spiders, scorpions, snakes, frogs, and fishes are therefore not mere curiosities but valuable tools for research on the molecular mechanisms of neural function and synaptic transmission.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0952-3499
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The present paper reports the preparation and characterization of two neutralizing monoclonal antibodies (Mabs), called MST1 and MST2, which bind at the central loop of a long-chain neurotoxin from cobra venom. The central loop is a critical region for the binding of the toxin to the nicotinic acetylcholine receptor. Some of the residues incorporated in the epitopes recognized by MST1 and MST2 have been identified on the basis of competition experiments using a set of ‘chemical mutants’ of the toxin. We show that MST1 and MST2 bind at the base and at the tip of the central loop of the toxin, respectively, however, only MST2 actually overlaps the acetylcholine receptor binding site. Accordingly, only MST2 is capable of recognizing all homologous toxins so far examined. MST2, therefore, mimicks, at least partially, the site by which the nicotinic acetylcholine receptor recognizes a long-chain neurotoxin.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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