title: Unexpected sensitivity of the human alpha7 neuronal nicotinic acetylcholine receptor to aminoglycosides.
abstract: The wide use of antibiotics and the development of resistance is a major health concern and, despite their relatively severe side effects, aminoglycoside antibiotics are still used in clinics. Effects of seven aminoglycosides were investigated at the human homomeric alpha7 and heteromeric alpha4beta2 neuronal nicotinic acetylcholine receptors. All aminoglycosides tested inhibited the acetylcholine-evoked responses with more pronounced effects at alpha7 than at alpha4beta2. Neomycin displayed higher blockade with a half inhibition in the nanomolar range at low calcium concentration and in the micromolar range in physiological calcium concentration but still exerted blockade below the concentration used in the clinic. These data suggest that some of their side effects may be attributable to their interactions with neuronal nicotinic acetylcholine receptors.
authors.affiliation: Department of Neuroscience, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Hoda
authors.forename: Ryoko
authors.initials: R
authors.lastname: Krause
authors.forename: Sonia
authors.initials: S
authors.lastname: Bertrand
authors.forename: Daniel
authors.initials: D
authors.lastname: Bertrand
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000617:Aminoglycosides / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002038:Bungarotoxins / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008845:Microinjections / Q000379:methods; D009355:Neomycin / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D011869:Radioligand Assay / Q000379:methods; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D002038:Bungarotoxins; C579167:Chrna7 protein, human; D007456:Iodine Isotopes; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; D009355:Neomycin; D000109:Acetylcholine