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Interaction of carvacrol with the Ascaris suum nicotinic acetylcholine receptors and gamma-aminobutyric acid receptors, potential mechanism of antinematodal action
- Trailović, Saša M., Marjanović, Djordje S., Nedeljković Trailović, Jelena, Robertson, Alan P., Martin, Richard J.
- Parasitology research 2015 v.114 no.8 pp. 3059-3068
- Ascaris suum, acetylcholine, carvacrol, cholinergic receptors, gamma-aminobutyric acid, gamma-aminobutyric acid receptors, membrane potential, muscles, nematicides, piperazine, plant fats and oils
- Essential plant oils (or their active principles) are safe to use and a potentially attractive alternative to current antiparasitic drugs. In the present study, we tested the effects of carvacrol on the isolated tissues of Ascaris suum and investigated potential interactions with other antiparasitic drugs. We used somatic muscle flaps for contraction assays, as well as for electrophysiological investigations. Carvacrol 300 μM highly significantly inhibited contractions caused by 1, 3, 10, 30, and 100 μM of ACh (p = 0.0023, p = 0.0002, p = 0.0002, p < 0.0001, and p < 0.0001). The control EC₅₀ for acetylcholine was 8.87 μM (log EC₅₀ = 0.95 ± 0.26), while R ₘₐₓ was 2.53 ± 0.24 g. The EC₅₀ of acetylcholine in the presence of 300 μM of carvacrol was 27.71 μM (log EC₅₀ = 1.44 ± 0.28) and the R ₘₐₓ decreased to 1.63 ± 0.32 g. Furthermore, carvacrol highly significant potentiates inhibitory effect of GABA and piperazine on the contractions induced by ACh. However, carvacrol (100 and 300 μM), did not produce any changes in the membrane potential or conductance of the A. suum muscle cell. While, 300 μM of carvacrol showed a significant inhibitory effect on ACh-induced depolarization response. The mean control depolarization was 13.58 ± 0.66 mV and decreased in presence of carvacrol to 4.50 ± 1.02 mV (p < 0.0001). Mean control Δg was 0.168 ± 0.017 μS, while in the presence of 300 μM of carvacrol, Δg significantly decreased to 0.060 ± 0.018 ΔS (p = 0.0017). The inhibitory effect on contractions may be the explanation of the antinematodal potential of carvacrol. Moreover, inhibition of depolarizations caused by ACh and reduction of conductance changes directly points to an interaction with the nAChR in A. suum.