Levamisole binding sites in Haemonchus contortus.
Larval and adult extracts from isolates of Haemonchus contortus were assayed for specific [3H]levamisole binding activity. All of the tissue preparations displayed [3H]levamisole binding sites. The sensitive isolate SE and resistant isolate RJ showed no differences in larval and adult binding data. Larval SE extracts had higher receptor density (Bmax = 648 fmol mg-1) and dissociation constant (Kd = 1.28 microM) for [3H]levamisole than larval extracts of the American isolate RUSA (Bmax = 87 fmol mg-1 and Kd = 0.15 microM). Extracts of adult SE and RUSA isolates contain as much as 327 fmol mg-1 of protein and 205 fmol mg-1 of protein, respectively, and similar dissociation constants (Kd = 0.77 microM and Kd = 0.81 microM, respectively). There was a good correlation between specific binding activity of larval and adult extracts in both SE and RUSA isolates. The nicotinic cholinergic antagonist alpha-bungarotoxin had no effects in either isolate on [3H]levamisole binding activity. The results confirm that levamisole acts at a cholinergic receptor in H. contortus, and suggest that target site modification could be involved in the development of levamisole resistance.
Moreno-Guzmán
M J
MJ
Parasitology and Microbiology Department, Faculty of Pharmacy, University of Alcalá, Alcalá de Henares, Madrid, Spain. mpmjmg@microb.alcala.es
Coles
G C
GC
Jiménez-González
A
A
Criado-Fornelio
A
A
Ros-Moreno
R M
RM
Rodríguez-Caabeiro
F
F
D000818:Animals; D000969:Antinematodal Agents / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D002038:Bungarotoxins / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004351:Drug Resistance / Q000502:physiology; D005243:Feces / Q000469:parasitology; D006189:Haemonchus / Q000187:drug effects / Q000378:metabolism*; D007978:Levamisole / Q000378:metabolism* / Q000494:pharmacology; D010270:Parasite Egg Count; D011950:Receptors, Cholinergic / Q000378:metabolism* / Q000502:physiology; D012756:Sheep
D000969:Antinematodal Agents; D002038:Bungarotoxins; D018680:Cholinergic Antagonists; D011950:Receptors, Cholinergic; D007978:Levamisole