Ivermectin: A Positive Allosteric Effector of the α7 Neuronal Nicotinic Acetylcholine Receptor

• DOI: 10.1124/mol.53.2.283
• Publication Date: 2018-01-08T20:29:28Z
• Authors: Ryoko M. Krause; Bruno Buisson; Sonia Bertrand; Pierre-Jean Corri...; Jean-Luc Galzi; Jean-Pierre Changeux; Daniel Bertrand
• Keywords: Models, Molecular; 0301 basic medicine; [SDV]Life Sciences [q-bio]; MESH: Neurons; Receptors, Nicotinic; MESH: Allosteric Regulation; Membrane Potentials; MESH: Recombinant Proteins; MESH: Structure-Activity Relationship; MESH: Animals; Nicotinic Agonists; Anthelmintics; Neurons; MESH: Chickens; [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences; Recombinant Proteins; 3. Good health; [SDV] Life Sciences [q-bio]; [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences; MESH: Anthelmintics; [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology; MESH: Receptors, Nicotinic; Ion Channel Gating; MESH: Models, Molecular; MESH: Ivermectin; MESH: Oocytes; Cell Line; MESH: alpha7 Nicotinic Acetylcholine Receptor; 03 medical and health sciences; Allosteric Regulation; MESH: Xenopus laevis; Chloride Channels; MESH: Nicotinic Agonists; MESH: Membrane Potentials; Animals; Humans; Point Mutation; MESH: Point Mutation; MESH: Humans; Binding Sites; Ivermectin; MESH: Transfection; MESH: Chloride Channels; Cell Membrane; MESH: Ion Channel Gating; MESH: Cell Line; MESH: Solubility; MESH: Binding Sites; Solubility; [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology; Oocytes; Chickens; MESH: Cell Membrane

We report that preapplication of ivermectin, in the micromolar range, strongly enhances subsequent acetylcholine-evoked current neuronal chick or human α7 nicotinic acetylcholine receptors reconstituted <i>Xenopus laevis</i> oocytes and K-28 cells. This potentiation does not result from nonspecific Cl⁻currents. The concomitant increase apparent affinity cooperativity dose-response curve suggest ivermectin acts as a positive allosteric effector. interpretation is supported by observation an efficiency partial agonist associated with differential effect on mutants within M2 channel domain. Ivermectin effects reveal novel site for pharmacological agents receptors.