Characterization of an acetylcholine receptor gene of Haemonchus contortus in relation to levamisole resistance.
The anthelminitic drug levamisole is thought to bind to nicotinic acetylcholine receptors of nematodes. It is possible that resistance to this drug is associated with either a change in binding characteristics or a reduction in the number of nicotinic acetylcholine receptors. Therefore, the molecular mechanism of levamisole resistance in the parasitic nematode Haemonchus contortus was studied by isolating and characterising cDNA clones encoding a putative ligand binding nicotinic acetylcholine receptor subunit, HCAl, of two susceptible and one levamisole resistant population. Hcal is related to unc-38, a nicotinic acetylcholine receptor subunit gene associated with levamisole resistance in Caenorhabditis elegans. Although extensive sequence analyses of hcal sequences revealed polymorphism at amino acid level, no association with levamisole resistance could be detected. Restriction fragment length polymorphism analyses confirmed that, although polymorphism was detected, no selection of a specific allele of hcal has taken place during selection for levamisole resistance in various levamisole resistant populations.
Hoekstra
R
R
Department of Molecular Recognition, Institute for Animal Science and Health (ID-DLO), Lelystad, The Netherlands.
Visser
A
A
Wiley
L J
LJ
Weiss
A S
AS
Sangster
N C
NC
Roos
M H
MH
D000595:Amino Acid Sequence; D000818:Animals; D000969:Antinematodal Agents / Q000378:metabolism / Q000494:pharmacology*; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D018509:DNA, Helminth / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D017238:Genes, Helminth; D006189:Haemonchus / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D007978:Levamisole / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D000969:Antinematodal Agents; D017931:DNA Primers; D018076:DNA, Complementary; D018509:DNA, Helminth; D011978:Receptors, Nicotinic; D007978:Levamisole