6533b85cfe1ef96bd12bd517
RESEARCH PRODUCT
α-Conotoxins EpI and AuIB switch subtype selectivity and activity in native versus recombinant nicotinic acetylcholine receptors
Marion L. LoughnanRichard J. LewisAnnette NickeAlfred MaelickeParamjit S. BansalMarek Samochockisubject
α7 nicotinic acetylcholine receptorα-Conotoxin AuIBRecombinant Fusion ProteinsBiophysicsXenopusNicotinic AntagonistsReceptors NicotinicPharmacologyTransfectionBiochemistrycomplex mixturesSubstrate SpecificityInhibitory Concentration 50Xenopus laevisStructural BiologyGeneticsmedicineAnimalsConotoxinNicotinic AntagonistReceptorMolecular BiologyAcetylcholine receptorbiologyα-Conotoxin EpICell Biologybiology.organism_classificationRatsCell biologyProtein SubunitsNicotinic acetylcholine receptorNicotinic agonistnervous systemIntracardiac gangliaOocytessense organsReceptors Serotonin 5-HT3ConotoxinsAcetylcholineXenopus laevis oocytemedicine.drugdescription
The Xenopus laevis oocyte expression system was used to determine the activities of alpha-conotoxins EpI and the ribbon isomer of AuIB, on defined nicotinic acetylcholine receptors (nAChRs). In contrast to previous findings on intracardiac ganglion neurones, alpha-EpI showed no significant activity on oocyte-expressed alpha3beta4 and alpha3beta2 nAChRs but blocked the alpha7 nAChR with an IC50 value of 30 nM. A similar IC50 value (103 nM) was obtained on the alpha7/5HT3 chimeric receptor stably expressed in mammalian cells. Ribbon AuIB maintained its selectivity on oocyte-expressed alpha3beta4 receptors but unlike in native cells, where it was 10-fold more potent than native alpha-AuIB, had 25-fold lower activity. These results indicate that as yet unidentified factors influence alpha-conotoxin pharmacology at native versus oocyte-expressed nAChRs.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2003-11-05 | FEBS Letters |