Interaction of ivermectin with γ-aminobutyric acid receptors in Trichinella spiralis muscle larvae.

The value of the γ-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 ( K_d) of 83 n M and a receptor density (B_max) of 145 fmol/mg protein. We also identified a specific [³H]-GABA binding activity with a K_d of 1.2 μ M and a B_max 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 n M, suggesting that GABA receptors could be implicated in the mechanism of action of ivermectin in nematodes. [ABSTRACT FROM AUTHOR]