title: Binding of [3H]m-aminolevamisole to receptors in levamisole-susceptible and -resistant Haemonchus contortus.
abstract: M-aminolevamisole, a potent analogue of the commercial anthelmintic levamisole, was used to investigate ligand-binding properties of homogenates of larval and parasitic stages of the nematode parasite of sheep, Haemonchus contortus. Kinetics of the binding of [3H]m-aminolevamisole to homogenates was measured in a drug-susceptible isolate and compared with a levamisole-resistant isolate. Equilibrium binding studies and kinetic studies revealed a high affinity binding component with a KD of 3 nM. A low affinity component (KD = 2.4 microM) was also apparent in equilibrium studies. High affinity [3H]m-aminolevamisole binding was displaced in a concentration-dependent manner by levamisole analogues and cholinergic agonists. Compared with the susceptible isolate, binding in a levamisole-resistant isolate of the parasite, was quantitatively similar over a range of developmental stages and binding conditions. However, under the conditions of binding there was a reduced affinity (larger KD) and more binding sites (larger Bmax) at the low affinity site in the resistant compared with the susceptible isolate. It was concluded that the ligand was binding to acetylcholine receptor populations of the nematode and that resistance may be associated with alterations in the low affinity site of this receptor.
authors.affiliation: Department of Veterinary Anatomy and Pathology, University of Sydney, N.S.W., Australia. n.sangster@vetp.usyd.edu.au
authors.forename: N C
authors.initials: NC
authors.lastname: Sangster
authors.forename: F L
authors.initials: FL
authors.lastname: Riley
authors.forename: L J
authors.initials: LJ
authors.lastname: Wiley
mesh_terms: D000818:Animals; D000969:Antinematodal Agents / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D004351:Drug Resistance; D006189:Haemonchus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D007978:Levamisole / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D008024:Ligands; D009119:Muscle Contraction / Q000187:drug effects; D010270:Parasite Egg Count; D019920:Photoaffinity Labels; D011950:Receptors, Cholinergic / Q000378:metabolism*
chemical_list: D000969:Antinematodal Agents; D008024:Ligands; D019920:Photoaffinity Labels; D011950:Receptors, Cholinergic; D007978:Levamisole; C051392:3-aminolevamisole