Interaction of ivermectin with gamma-aminobutyric acid receptors in Trichinella spiralis muscle larvae.
Parasitology research
confidence
Key findings
Ivermectin binds T. spiralis larvae (Kd 83 nM) and competitively inhibits GABA binding (Ki 3.39 nM), implicating GABA receptors in its mechanism.
View source on PubMed (PMID 10099015) ↗
- Sample size
- Not reported
- Population
- Trichinella spiralis muscle larvae (in vitro tissue extracts)
- Dosing
- Not applicable (binding assay concentrations)
- Duration
- Not applicable
- Route
- In vitro
- Blinding
- not_reported
- Controls
- none
- Drug class
- antiparasitic
Full abstract
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.