title: Emamectin is a non-selective allosteric activator of nicotinic acetylcholine receptors and GABAA/C receptors.
abstract: Avermectins are a group of compounds isolated from a soil-dwelling bacterium. They have been widely used as parasiticides and insecticides, acting by relatively irreversible activation of invertebrate chloride channels. Emamectin is a soluble derivative of an avermectin. It is an insecticide, which persistently activates glutamate-gated chloride channels. However, its effects on mammalian ligand-gated ion channels are unknown. To this end, we tested the effect of emamectin on two cation selective nicotinic receptors and two GABA-gated chloride channels expressed in Xenopus oocytes using two-electrode voltage clamp. Our results demonstrate that emamectin could directly activate α7 nAChR, α4β2 nAChR, α1β2γ2 GABAA receptor and ρ1 GABAC receptor concentration dependently, with similar potencies for each channel. However, the potencies for it to activate these channels were at least two orders of magnitude lower than its potency of activating invertebrate glutamate-gated chloride channel. In contrast, ivermectin only activated the α1β2γ2 GABAA receptor.
authors.affiliation: Institute of Pesticide and Environmental Toxicology, Zhejiang University, Hangzhou, Zhejiang Province 310029, China; Division of Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Barrett, The Honors College, Arizona State University, Tempe, AZ 85281, USA.
authors.forename: Caraline
authors.initials: C
authors.lastname: Sepich
authors.affiliation: Division of Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Lukas
authors.affiliation: Institute of Pesticide and Environmental Toxicology, Zhejiang University, Hangzhou, Zhejiang Province 310029, China.
authors.forename: Guonian
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Division of Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA. Electronic address: Yongchang.chang@dignityhealth.org.
authors.forename: Yongchang
authors.initials: Y
authors.lastname: Chang
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D004187:Disaccharides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007306:Insecticides / Q000494:pharmacology; D015640:Ion Channel Gating / Q000502:physiology*; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018722:Nicotinic Agonists; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018079:Receptors, GABA / Q000187:drug effects* / Q000378:metabolism; D011963:Receptors, GABA-A; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D004187:Disaccharides; C087200:GABA-C receptor; D007306:Insecticides; D018722:Nicotinic Agonists; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D011978:Receptors, Nicotinic; D007559:Ivermectin; C443359:emamectin
keywords: Allosteric activation; Emamectin; GABA(A/C) receptor; Ivermectin; Nicotinic receptor