Menthol acts as a positive allosteric modulator on nematode levamisole sensitive nicotinic acetylcholine receptors
2019
Аутори
Choudhary, ShivaniMarjanović, Đorđe
Wong, Colin R.
Zhang, Xiaoyu
Abongwa, Melanie
Coats, Joel R.
Trailović, Saša
Martin, Richard J.
Robertson, Alan P.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 re...vealed 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.
Кључне речи:
Menthol / Allosteric modulation / nAChR / Monoterpenoid / NematodeИзвор:
International Journal for Parasitology-Drugs and Drug Resistance, 2019, 9, 44-53Издавач:
- Elsevier Sci Ltd, Oxford
Финансирање / пројекти:
- NIH National Institute of Allergy and Infectious DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R21AI121831-01, R01AI047194-17]
- College of Veterinary Medicine TA
- Iowa Agricultural Experiment Station
- Развој биљних лекова и биоцида на бази карвакрола, тимола и цинамалдехида за примену у ветеринарској медицини, сточарству и производњи хране без штетних резидуа (RS-31087)
DOI: 10.1016/j.ijpddr.2018.12.005
ISSN: 2211-3207
PubMed: 30682641
WoS: 000462490500007
Scopus: 2-s2.0-85060995747
Колекције
Институција/група
Fakultet veterinarske medicineTY - 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 . .