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  Waglerin-1 selectively blocks the epsilon form of the muscle nicotinic acetylcholine receptor

McArdle, J. J., Lentz, T. L., Witzemann, V., Schwarz, H., Weinstein, S. A., & Schmidt, J. J. (1999). Waglerin-1 selectively blocks the epsilon form of the muscle nicotinic acetylcholine receptor. Journal of Pharmacology and Experimental Therapeutics, 289(1), 543-550. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10087048.

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JPharmacolExpTherap_289_1999_543.pdf (beliebiger Volltext), 313KB
 
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McArdle, Joseph J., Autor
Lentz, Thomas L., Autor
Witzemann, Veit1, 2, Autor           
Schwarz, Holger2, Autor           
Weinstein, Scott A., Autor
Schmidt, James J., Autor
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              
2Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497701              

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 Zusammenfassung: Neonatal mice resist the lethal effect of Waglerin-1. Because Waglerin-1 blocks the nicotinic acetylcholine receptor of mature end-plates, the appearance of lethality may result from the epsilon - for gamma -subunit substitution. In support of this hypothesis, adult knockout (KO) mice lacking the gene coding for the epsilon -subunit resist the lethal effect of Waglerin-1. In contrast, heterozygous litter mates respond to Waglerin-1 like adult wild-type mice. In vitro application of 1 ?M Waglerin-1 inhibited spontaneous miniature end-plate potentials and evoked end-plate potentials of adult wild-type and heterozygous KO mice. Both miniature end-plate potentials and end-plate potentials of neonatal wild-type and adult homozygous KO mice resisted Waglerin-1. Waglerin-1 decreased the end-plate response of adult wild-type mice to iontophoretically applied acetylcholine (ACh) with an IC50 value of 50 nM; 1 ?M Waglerin-1 decreased the ACh response to 4 ? 1% of control for adult heterozygous KO mice. In contrast, 1 ?M Waglerin-1 decreased the ACh response to 73 ? 2% of control for wild-type mice less than 11 days old and had no effect on the ACh response of adult homozygous KO mice. Between 11 and 12 days after birth, the suppressant effect of Waglerin-1 on wild-type end-plate responses to ACh dramatically increased. Waglerin-1 reduced binding of alpha -bungarotoxin to end-plates of adult but not neonatal wild-type mice. These data demonstrate that Waglerin-1 selectively blocks the mouse muscle nicotinic acetylcholine receptor containing the epsilon -subunit

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Sprache(n): eng - English
 Datum: 1998-09-191998-11-231999-04-01
 Publikationsstatus: Erschienen
 Seiten: 8
 Ort, Verlag, Ausgabe: -
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 Art der Begutachtung: Expertenbegutachtung
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Titel: Journal of Pharmacology and Experimental Therapeutics
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: Bethesda, Md. : American Society for Pharmacology and Experimental Therapeutics
Seiten: - Band / Heft: 289 (1) Artikelnummer: - Start- / Endseite: 543 - 550 Identifikator: ISSN: 0022-3565
CoNE: https://pure.mpg.de/cone/journals/resource/954925432383