Interaction of ivermectin with gamma-aminobutyric acid receptors in Trichinella spiralis muscle larvae.
The value of the gamma-aminobutyric acid (GABA) receptor of nematodes as a target for ivermectin's mode of action remains unclear. Using binding assays, we examined extracts from Trichinella spiralis muscle larvae for the presence of [3H]-ivermectin and [3H]-GABA binding sites. Tissue preparations displayed affinity binding sites for [3H]-ivermectin with a dissociation constant (Kd) of 83 nM and a receptor density (Bmax) of 145 fmol/mg protein. We also identified a specific [3H]-GABA binding activity with a Kd of 1.2 microM and a Bmax of 4.78 pmol/mg protein. In competition studies, ivermectin was found to be a competitive inhibitor of specific [3H]-GABA binding activity with an inhibition constant (K(i)) of 3.39 nM, suggesting that GABA receptors could be implicated in the mechanism of action of ivermectin in nematodes.
Ros-Moreno
R M
RM
Parasitology and Microbiology Department, Faculty of Pharmacy, University of Alcalá, Alcalá de Henares (Madrid), Spain. mpcas@microb.alcala.es
Moreno-Guzmán
M J
MJ
Jiménez-González
A
A
Rodríguez-Caabeiro
F
F
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D007559:Ivermectin / Q000378:metabolism*; D007814:Larva / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism*; D017160:Trichinella spiralis / Q000254:growth & development / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; D007559:Ivermectin