2024-03-28T09:03:57Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/161232021-12-27T16:19:12Zcom_10261_5063com_10261_5col_10261_5066
2009-08-21T07:31:29Z
urn:hdl:10261/16123
A uniquely selective inhibitor of the mammalian fetal neuromuscular nicotinic acetylcholine receptor
Teichert, Russell W.
Rivier, Jean
Torres, Josep Lluís
Dykert, John
Miller, Charleen
Olivera, Baldomero M.
Fetal
Muscle
nAChR
Acetylcholine
Inhibitor
Receptor
5 pages, 4 figures.-- PMID: 15659611 [PubMed].
We 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.
2009-08-21T07:31:29Z
2009-08-21T07:31:29Z
2005-01-19
artículo
Journal of Neuroscience 25(3): 732-736 (2005)
0270-6474
http://hdl.handle.net/10261/16123
10.1523/JNEUROSCI.4065-04.2005
1529-2401
15659611
eng
http://dx.doi.org/10.1523/JNEUROSCI.4065-04.2005
closedAccess
Society for Neuroscience