α-Conotoxins EpI and AuIB switch subtype selectivity and activity in native versus recombinant nicotinic acetylcholine receptors

• Published in: FEBS letters Vol. 554; no. 1-2; pp. 219 - 223
• Main Authors: Nicke, Annette, Samochocki, Marek, Loughnan, Marion L, Bansal, Paramjit S, Maelicke, Alfred, Lewis, Richard J
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 06.11.2003
• Subjects: ACh, acetylcholine; Animals; Conotoxins - pharmacology; Inhibitory Concentration 50; Intracardiac ganglia; nAChR, nicotinic acetylcholine receptor; Nicotinic Antagonists - pharmacology; Oocytes; Protein Subunits - drug effects; Rats; Receptors, Nicotinic - drug effects; Receptors, Nicotinic - genetics; Receptors, Serotonin, 5-HT3 - drug effects; Receptors, Serotonin, 5-HT3 - genetics; Recombinant Fusion Proteins - drug effects; Recombinant Fusion Proteins - genetics; Substrate Specificity; Transfection; Xenopus laevis; Xenopus laevis oocyte; α-BTX, α-bungarotoxin; α-Conotoxin AuIB; α-Conotoxin EpI; α7 nicotinic acetylcholine receptor; α-BTX; α-Conotoxin AuIB; nAChR; ACh; Intracardiac ganglia; Xenopus laevis oocyte; α-Conotoxin EpI; α7 nicotinic acetylcholine receptor
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(03)01161-X

The Xenopus laevis oocyte expression system was used to determine the activities of α-conotoxins EpI and the ribbon isomer of AuIB, on defined nicotinic acetylcholine receptors (nAChRs). In contrast to previous findings on intracardiac ganglion neurones, α-EpI showed no significant activity on oocyte-expressed α3β4 and α3β2 nAChRs but blocked the α7 nAChR with an IC50 value of 30 nM. A similar IC50 value (103 nM) was obtained on the α7/5HT3 chimeric receptor stably expressed in mammalian cells. Ribbon AuIB maintained its selectivity on oocyte-expressed α3β4 receptors but unlike in native cells, where it was 10-fold more potent than native α-AuIB, had 25-fold lower activity. These results indicate that as yet unidentified factors influence α-conotoxin pharmacology at native versus oocyte-expressed nAChRs.