TY  - JOUR
AU  - Choudhary, Shivani
AU  - Marjanović, Đorđe
AU  - Wong, Colin R.
AU  - Zhang, Xiaoyu
AU  - Abongwa, Melanie
AU  - Coats, Joel R.
AU  - Trailović, Saša
AU  - Martin, Richard J.
AU  - Robertson, Alan P.
PY  - 2019
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/1730
AB  - The ongoing and widespread emergence of resistance to the existing anti-nematodal pharmacopeia has made it imperative to develop new anthelminthic agents. Historically, plants have been important sources of therapeutic compounds and offer an alternative to synthetic drugs. Monoterpenoids are phytochemicals that have been shown to produce acute toxic effects in insects and nematodes. Previous studies have shown nicotinic acetylcholine receptors (nAChRs) to be possible targets for naturally occurring plant metabolites such as carvacrol and carveol. In this study we examined the effects of monoterpenoid compounds on a levamisole sensitive nAChR from Oesophagostomum dentatum and a nicotine sensitive nAChR from Ascaris suum. We expressed the receptors in Xenopus laevis oocytes and used two-electrode voltage-clamp to characterize the effect of various compounds on these cys-loop receptors. At 100 mu M the majority of these compounds acted as antagonists. Interestingly, further experiments revealed that both 0.1 mu M and 10 mu M menthol potentiated acetylcholine and levamisole responses in the levamisole sensitive receptor but not the nicotine sensitive receptor. We also investigated the effects of 0.1 mu M menthol on the contractility of A. suum somatic muscle strips. Menthol produced significant potentiation of peak contractions at each concentration of acetylcholine. The positive allosteric modulatory effects of menthol in both in vivo and in vitro experiments suggests menthol as a promising candidate for combination therapy with cholinergic anthelmintics.
PB  - Elsevier Sci Ltd, Oxford
T2  - International Journal for Parasitology-Drugs and Drug Resistance
T1  - Menthol acts as a positive allosteric modulator on nematode levamisole sensitive nicotinic acetylcholine receptors
VL  - 9
SP  - 44
EP  - 53
DO  - 10.1016/j.ijpddr.2018.12.005
ER  - 

@article{
author = "Choudhary, Shivani and Marjanović, Đorđe and Wong, Colin R. and Zhang, Xiaoyu and Abongwa, Melanie and Coats, Joel R. and Trailović, Saša and Martin, Richard J. and Robertson, Alan P.",
year = "2019",
abstract = "The ongoing and widespread emergence of resistance to the existing anti-nematodal pharmacopeia has made it imperative to develop new anthelminthic agents. Historically, plants have been important sources of therapeutic compounds and offer an alternative to synthetic drugs. Monoterpenoids are phytochemicals that have been shown to produce acute toxic effects in insects and nematodes. Previous studies have shown nicotinic acetylcholine receptors (nAChRs) to be possible targets for naturally occurring plant metabolites such as carvacrol and carveol. In this study we examined the effects of monoterpenoid compounds on a levamisole sensitive nAChR from Oesophagostomum dentatum and a nicotine sensitive nAChR from Ascaris suum. We expressed the receptors in Xenopus laevis oocytes and used two-electrode voltage-clamp to characterize the effect of various compounds on these cys-loop receptors. At 100 mu M the majority of these compounds acted as antagonists. Interestingly, further experiments revealed that both 0.1 mu M and 10 mu M menthol potentiated acetylcholine and levamisole responses in the levamisole sensitive receptor but not the nicotine sensitive receptor. We also investigated the effects of 0.1 mu M menthol on the contractility of A. suum somatic muscle strips. Menthol produced significant potentiation of peak contractions at each concentration of acetylcholine. The positive allosteric modulatory effects of menthol in both in vivo and in vitro experiments suggests menthol as a promising candidate for combination therapy with cholinergic anthelmintics.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "International Journal for Parasitology-Drugs and Drug Resistance",
title = "Menthol acts as a positive allosteric modulator on nematode levamisole sensitive nicotinic acetylcholine receptors",
volume = "9",
pages = "44-53",
doi = "10.1016/j.ijpddr.2018.12.005"
}

Choudhary, S., Marjanović, Đ., Wong, C. R., Zhang, X., Abongwa, M., Coats, J. R., Trailović, S., Martin, R. J.,& Robertson, A. P.. (2019). Menthol acts as a positive allosteric modulator on nematode levamisole sensitive nicotinic acetylcholine receptors. in International Journal for Parasitology-Drugs and Drug Resistance
Elsevier Sci Ltd, Oxford., 9, 44-53.
https://doi.org/10.1016/j.ijpddr.2018.12.005

Choudhary S, Marjanović Đ, Wong CR, Zhang X, Abongwa M, Coats JR, Trailović S, Martin RJ, Robertson AP. Menthol acts as a positive allosteric modulator on nematode levamisole sensitive nicotinic acetylcholine receptors. in International Journal for Parasitology-Drugs and Drug Resistance. 2019;9:44-53.
doi:10.1016/j.ijpddr.2018.12.005 .

Choudhary, Shivani, Marjanović, Đorđe, Wong, Colin R., Zhang, Xiaoyu, Abongwa, Melanie, Coats, Joel R., Trailović, Saša, Martin, Richard J., Robertson, Alan P., "Menthol acts as a positive allosteric modulator on nematode levamisole sensitive nicotinic acetylcholine receptors" in International Journal for Parasitology-Drugs and Drug Resistance, 9 (2019):44-53,
https://doi.org/10.1016/j.ijpddr.2018.12.005 . .