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Título

A uniquely selective inhibitor of the mammalian fetal neuromuscular nicotinic acetylcholine receptor

AutorTeichert, Russell W.; Rivier, Jean; Torres, Josep Lluís; Dykert, John; Miller, Charleen; Olivera, Baldomero M.
Palabras claveFetal
Muscle
nAChR
Acetylcholine
Inhibitor
Receptor
Fecha de publicación19-ene-2005
EditorSociety for Neuroscience
CitaciónJournal of Neuroscience 25(3): 732-736 (2005)
ResumenWe have purified and characterized a novel conotoxin from the venom of Conus obscurus, which has the unique property of selectively and potently inhibiting the fetal form of the mammalian neuromuscular nicotinic acetylcholine receptor (nAChR) ({alpha}1{beta}1{gamma}{delta}-subunits). Although this conotoxin, {alpha}A-conotoxin OIVB ({alpha}A-OIVB), is a high-affinity antagonist (IC50 of 56 nM) of the fetal muscle nAChR, it has >1800-fold lower affinity for the adult muscle nAChR ({alpha}1{beta}1{epsilon}{delta}-subunits) and virtually no inhibitory activity at a high concentration on various neuronal nAChRs (IC50 > 100 µM in all cases). The peptide (amino acid sequence, CCGVONAACPOCVCNKTCG), with three disulfide bonds, has been chemically synthesized in a biologically active form. Although the neuromuscular nAChRs are perhaps the most extensively characterized of the receptors/ion channels of the nervous system, the precise physiological roles of the fetal form of the muscle nAChR are essentially unknown.{alpha}A-OIVB is a potentially important tool for delineating the functional roles of{alpha}1{beta}1{gamma}{delta} receptors in normal development, as well as in various adult tissues and in pathological states. In addition to its potential as a research tool, {alpha}A-OIVB may have some direct biomedical applications.
Descripción5 pages, 4 figures.-- PMID: 15659611 [PubMed].
Versión del editorhttp://dx.doi.org/10.1523/JNEUROSCI.4065-04.2005
URIhttp://hdl.handle.net/10261/16123
DOI10.1523/JNEUROSCI.4065-04.2005
ISSN0270-6474 (Print)
1529-2401 (Online)
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