Caenorhabditis elegans ivermectin receptors regulate locomotor behaviour and are functional orthologues of Haemonchus contortus receptors

Molecular and Biochemical Parasitology
Alan CookAdrian J Wolstenholme

Abstract

The target site for the anthelmintic action of ivermectin is a family of nematode glutamate-gated chloride channel alpha subunits (GluClalpha) that bind the drug with high affinity and mediate its potent paralytic action. Whilst the action of ivermectin on the pharyngeal muscle of nematodes is relatively well understood, its effect on locomotor activity is less clear. Here we use RNAi and gene knockouts to show that four GluClalpha subunits are involved in regulating the pattern of locomotor activity in Caenorhabditis elegans. A Haemonchus contortus orthologue of these subunits, HcGluClalpha3, has been shown to be expressed in the motor nervous system and here we have shown that it is a functional, as well as a structural, orthologue by virtue of the observation that it can restore normal motor movement in the C. elegans GluClalpha mutant, avr-14(ad1032), when expressed under the control of the avr-14 promoter. This supports the contention that ivermectin exerts its paralytic action on parasitic nematodes through activation of GluCl channels in the motor nervous system. Furthermore, functional complementation in C. elegans provides a method to further the understanding of this important class of anthelmintic targets.

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Citations

Feb 22, 2008·Invertebrate Neuroscience : in·Andrew K Jones, David B Sattelle
Oct 6, 2012·The Journal of Biological Chemistry·Adrian J Wolstenholme
Jun 3, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ellena V McCarthyMichael N Nitabach
Jan 10, 2016·Molecular and Biochemical Parasitology·Megan A SloanAdrian J Wolstenholme
Jan 23, 2016·Proceedings of the National Academy of Sciences of the United States of America·Nurit Degani-KatzavYoav Paas
Jul 28, 2009·Veterinary Parasitology·Bernadette F ArdelliRoger K Prichard
Aug 23, 2011·Experimental Parasitology·Collette BrittonDavid P Knox
Sep 30, 2016·International Journal for Parasitology. Drugs and Drug Resistance·Thangadurai ManiRoger K Prichard
Nov 30, 2020·International Journal for Parasitology. Drugs and Drug Resistance·Steffen R HahnelDaniel Kulke

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Anthelmintics (ASM)

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.