Selective effects of a 4-oxystilbene derivative on wild and mutant neuronal chick al nicotinic receptor

Abstract

1 We assessed the pharmacological activity of triethyl-(/?-4-stilbenoxy-ethyl) ammonium (MG624), a drug that is active on neuronal nicotinic receptors (nicotinic AChR). Experiments on the major nicotinic AChR subtypes present in chick brain, showed that it inhibits the binding of [125I]Bungarotoxin (ccBgtx) to the a? subtype, and that of [3H]-epibatidine (Epi) to the a4/?2 subtype, with K-, values of respectively 106 nM and 84 / <5 chick subtype with an IC50 of 2.9/(M. 4 The interaction of MG624 with the a? subtype was investigated using an 7 homomeric mutant receptor with a threonine-for-leucine 247 substitution (L247T a7). MG624 did not induce any current in oocytes expressing the wild type al receptor, but did induce large currents in the oocyteexpressed L247T a.1 receptor. The MG624 elicited current (IMG62-i) has an EC50 of 0.2 nM and a Hill coefficient nH of 1.9, and is blocked by the nicotinic receptor antagonist methyllycaconitine (MLA). 5 These binding and electrophysiological studies show that MG624 is a potent antagonist of neuronal chick a 7 nicotinic AChR, and becomes a competitive agonist following the mutation of the highly conserved leucine residue 247 located in the M2 channel domain. © 1999 Stockton Press All rights reserved.