title: Macrolide compounds, ivermectin and milbemycin D, stimulate chloride channels sensitive to GABAergic drugs in cultured chick spinal neurons.
abstract: 1. The effects of ivermectin (IVM) and milbemycin D (MMD) on cultured embryonic spinal neurons were investigated, using the whole-cell recording technique. 2. IVM and MMD caused Cl- current under voltage-clamp conditions. 3. The reversal potential of the MMD-evoked Cl- current was shifted in a positive direction when half of the external Cl- was substituted by isethionate. 4. The MMD-evoked current was inhibited by picrotoxinin and bicuculline, whereas it was enhanced by diazepam. 5. Different characteristics of desensitization were observed between the MMD- (IVM-) and muscimol-induced effects. 6. These results suggest that IVM and MMD directly activate the Cl- channel through their specific sites modulated by GABAergic drugs.
authors: Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
authors: J
authors: J
authors: Yamazaki
authors: K
authors: K
authors: Matsumoto
authors: H
authors: H
authors: Ono
authors: H
authors: H
authors: Fukuda
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D002478:Cells, Cultured; D002642:Chick Embryo; D002712:Chlorides / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects*; D007559:Ivermectin / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology*; D018942:Macrolides; D008564:Membrane Potentials / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D010852:Picrotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D054830:Sesterterpenes; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001640:Bicuculline; D002712:Chlorides; D003975:Diazepam; D007473:Ion Channels; D007559:Ivermectin; D007783:Lactones; D018942:Macrolides; D009118:Muscimol; D010852:Picrotoxin; D054830:Sesterterpenes; D005680:gamma-Aminobutyric Acid; C022961:picrotoxinin; C027837:moxidectin