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Ivermectin binding sites in sensitive and resistant Haemonchus contortus
S P Rohrer1, E T Birzin, C H Eary
1Basic Animal Science Research, Merck Research Laboratories, Rahway, New Jersey 07065.
The Journal of Parasitology
|June 1, 1994
Summary
Ivermectin resistance in Haemonchus contortus is not due to changes in drug binding sites. Both sensitive and resistant nematodes show similar high-affinity ivermectin binding, suggesting other resistance mechanisms are at play.
Area of Science:
- Parasitology
- Molecular Pharmacology
- Veterinary Entomology
Background:
- Ivermectin is a crucial anthelmintic drug used to control parasitic infections in livestock.
- Drug resistance in nematodes, such as Haemonchus contortus, poses a significant threat to animal health and agricultural productivity.
- Understanding the molecular mechanisms of ivermectin resistance is essential for developing effective treatment strategies.
Purpose of the Study:
- To investigate the characteristics of ivermectin binding sites in both ivermectin-sensitive and -resistant Haemonchus contortus.
- To determine if alterations in the drug's target site contribute to ivermectin resistance in this nematode species.
Main Methods:
- Preparation of membranes from Haemonchus contortus L3 larvae (both sensitive and resistant strains).
- Radioligand binding assays using [3H]ivermectin to quantify high-affinity drug binding sites.
- Analysis of binding affinity (Kd) and receptor density (Bmax).
Main Results:
- High-affinity ivermectin binding sites were detected in both sensitive and resistant H. contortus larval membranes.
- The dissociation constant (Kd) was approximately 0.13 nM, indicating high drug affinity.
- Receptor density (Bmax) was consistent (0.4 pmol/mg) across both sensitive and resistant nematode preparations.
Conclusions:
- The ivermectin binding site in Haemonchus contortus exhibits similar characteristics (affinity and density) in both drug-sensitive and -resistant strains.
- Target site modification does not appear to be the primary mechanism for ivermectin resistance in this H. contortus strain.
- The findings suggest that alternative mechanisms, beyond alterations in the ivermectin binding site, are responsible for drug resistance in this nematode.