Alpha-conotoxins EpI and AuIB switch subtype selectivity and activity in native versus recombinant nicotinic acetylcholine receptors.
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.
Nicke
Annette
A
Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia.
Samochocki
Marek
M
Loughnan
Marion L
ML
Bansal
Paramjit S
PS
Maelicke
Alfred
A
Lewis
Richard J
RJ
D000818:Animals; D020916:Conotoxins / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009865:Oocytes; D021122:Protein Subunits / Q000187:drug effects; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics; D013379:Substrate Specificity; D014162:Transfection; D014982:Xenopus laevis
D020916:Conotoxins; D018733:Nicotinic Antagonists; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D044406:Receptors, Serotonin, 5-HT3; D011993:Recombinant Fusion Proteins