Journal
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 77, Issue -, Pages 78-86Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.ibmb.2016.08.005
Keywords
Ivermectin; GABA-gated chloride channel; Glutamate-gated chloride channel; Activation; Potentiation; Antagonism
Categories
Funding
- JSPS KAKENHI [26292031]
- Grants-in-Aid for Scientific Research [26292031] Funding Source: KAKEN
Ask authors/readers for more resources
Ivermectin (IVM) is a macrocyclic lactone that exerts antifilarial, antiparasitic, and insecticidal effects on nematodes and insects by acting on L-glutamic acid-gated chloride channels (GluCls). IVM also acts as an allosteric modulator of various other ion channels. Although the IVM binding site in the Caenorhabditis elegans GIuCl was identified by X-ray crystallographic analysis, the mechanism of action of IVM in insects is not well defined. We therefore examined the action of IVM on the housefly (Musca domestica) GIuCl and gamma-aminobutyric acid (GABA)-gated ion channel (GABACl). For both channels, IVM induced currents by itself, potentiated currents induced by low concentrations of agonists, and inhibited currents induced by high concentrations of agonists. Despite exerting common actions on both types of channels, GluCls were more susceptible to IVM actions than GABACls, indicating that GluCls are the primary target of IVM. Substitution of an amino acid residue in the third transmembrane segment (G312M in GluCls, and G333A and G333M in GABACls) resulted in significantly reduced levels or loss of activation, potentiation, and antagonism of the channels, indicating that these three actions result from the interaction of IVM with amino acid residues in the transmembrane intersubunit crevice. (C) 2016 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available