Anthelmintic actions on homomer-forming nicotinic acetylcholine receptor subunits: chicken alpha7 and ACR-16 from the nematode Caenorhabditis elegans

Neuroscience. 2000;101(3):785-91. doi: 10.1016/s0306-4522(00)00279-7.


Two homomer-forming nicotinic acetylcholine receptor subunits with 47% identity in their amino acid sequences were employed to compare the actions of cholinergic anthelmintics and ivermectin on expressed vertebrate and nematode nicotinic receptors of known molecular composition. Voltage-clamp electrophysiology was used to study recombinant nicotinic receptors expressed in Xenopus laevis oocytes following nuclear injection of cDNA encoding either chicken alpha7 or Caenorhabditis elegans ACR-16 (Ce21) subunits. Butamisole, morantel and metyridine were without agonist actions on either alpha7 or ACR-16 nicotinic receptors in the range 10nM-1mM. However, butamisole (pIC(50)=4.9 for both alpha7 and ACR-16) and morantel (pIC(50)=5.6 for alpha7 and 5.7 for ACR-16) antagonized responses of both alpha7 and ACR-16 receptors to acetylcholine. Metyridine (1mM) did not affect responses to acetylcholine of either receptor. Oxantel was without agonist actions on ACR-16, but was an acetylcholine antagonist (pIC(50)=5.4). In contrast, it was found to have low efficacy agonist action (pEC(50)=4.4) on alpha7 at concentrations in the range 10-300microM. In agreement with a previous study, ivermectin (30microM), an agonist of L-glutamate-gated chloride channels, enhanced the amplitude of responses to acetylcholine of alpha7 nicotinic receptors. However, this same concentration of ivermectin (30microM) did not potentiate the acetylcholine-induced responses of ACR-16, but rather resulted in a slight attenuation. We conclude that oxantel and ivermectin have identified new pharmacological differences between the chicken alpha7 nicotinic receptor and its C. elegans homologue ACR-16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Anthelmintics / pharmacology*
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Chickens / metabolism*
  • DNA, Complementary / drug effects
  • DNA, Complementary / physiology
  • Female
  • Ivermectin / pharmacology
  • Morantel / pharmacology
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Pyrantel / analogs & derivatives*
  • Pyrantel / pharmacology
  • Pyridines / pharmacology
  • Receptors, Nicotinic / chemistry
  • Receptors, Nicotinic / drug effects*
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / metabolism*
  • Sequence Homology*
  • Thiazoles / pharmacology
  • Xenopus laevis / metabolism
  • alpha7 Nicotinic Acetylcholine Receptor


  • Anthelmintics
  • Chrna7 protein, human
  • DNA, Complementary
  • Pyridines
  • Receptors, Nicotinic
  • Thiazoles
  • alpha7 Nicotinic Acetylcholine Receptor
  • methyridine
  • Pyrantel
  • Ivermectin
  • Morantel
  • oxantel
  • Acetylcholine
  • butamisole