Effects of monepantel on nicotinic acetylcholine receptors from Ascaris suum and Oesophagostomum dentatum
Само за регистроване кориснике
2016
Аутори
Trailović, SašaMarjanović, Đorđe
Tipton, James M.
Abongwa, Melanie
Zheng, Fudan
Choudhary, Shivani
Martin, Richard J.
Robertson, Alan P.
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Zolvix ® is a recently introduced anthelmintic drench containing monepantel as the active ingredient.
Monepantel has been demonstrated to act on deg-3/des-2 containing nAChRs in several nematodes as
a positive allosteric modulator. The drug produces hypercontraction of nematode muscle. We
investigated the effects of monepantel on muscle strips isolated form adult Ascaris suum. The drug did
not significantly increase baseline tension when applied on its own. Contractions induced by
acetylcholine and several cholininomimetic anthelmintics where antagonized by monepantel. Further
investigation revealed that the antagonism was non-competitive in nature. We also investigated the
effect of monepantel on nAChRs from O. dentatum heterologously expressed in Xenopus laevis
oocytes. We investigated the effects of monepantel on OD3, a levamisole preferring nAChR subtype,
OD4, a pyrantel preferring subtype and ACR-16 a nicotine preferring subtype. For each subtype tested
monepan...tel applied in isolation produced no measureable currents, nor did it produce currents in the
presence of choline. When monepantel was continuously applied it reduced the amplitude of
acetylcholine induced currents in a concentration dependent manner for the three nAChR subtypes
tested. In all three cases monepantel acted as a non-competitive antagonist on the expressed
receptors. ACR-16 was particularly sensitive to monepantel inhibition. Our findings suggest that the
mode of action of monepantel is more complex than previously described.
Кључне речи:
Zolvix / A.suum / O.dentatum / nAChR subtypesИзвор:
Antihelmintics : From discovery to resistance II, Captain’s Room: Marina Village Center: San Diego, CA- Feb. 9 - 12, 2016, 2016, 11-11Издавач:
- Society of Toxicology
Финансирање / пројекти:
- Развој биљних лекова и биоцида на бази карвакрола, тимола и цинамалдехида за примену у ветеринарској медицини, сточарству и производњи хране без штетних резидуа (RS-MESTD-Technological Development (TD or TR)-31087)
- Research grants: NIH RO1 A1047194 to RJM & APR, Schlumberger Faculty for the Future Fellowship to MA & APR. JT Support: NIH T35 OD 012199-13
Напомена:
- Book of Abstracts
Колекције
Институција/група
Fakultet veterinarske medicineTY - CONF AU - Trailović, Saša AU - Marjanović, Đorđe AU - Tipton, James M. AU - Abongwa, Melanie AU - Zheng, Fudan AU - Choudhary, Shivani AU - Martin, Richard J. AU - Robertson, Alan P. PY - 2016 UR - https://vet-erinar.vet.bg.ac.rs/handle/123456789/3346 AB - Zolvix ® is a recently introduced anthelmintic drench containing monepantel as the active ingredient. Monepantel has been demonstrated to act on deg-3/des-2 containing nAChRs in several nematodes as a positive allosteric modulator. The drug produces hypercontraction of nematode muscle. We investigated the effects of monepantel on muscle strips isolated form adult Ascaris suum. The drug did not significantly increase baseline tension when applied on its own. Contractions induced by acetylcholine and several cholininomimetic anthelmintics where antagonized by monepantel. Further investigation revealed that the antagonism was non-competitive in nature. We also investigated the effect of monepantel on nAChRs from O. dentatum heterologously expressed in Xenopus laevis oocytes. We investigated the effects of monepantel on OD3, a levamisole preferring nAChR subtype, OD4, a pyrantel preferring subtype and ACR-16 a nicotine preferring subtype. For each subtype tested monepantel applied in isolation produced no measureable currents, nor did it produce currents in the presence of choline. When monepantel was continuously applied it reduced the amplitude of acetylcholine induced currents in a concentration dependent manner for the three nAChR subtypes tested. In all three cases monepantel acted as a non-competitive antagonist on the expressed receptors. ACR-16 was particularly sensitive to monepantel inhibition. Our findings suggest that the mode of action of monepantel is more complex than previously described. PB - Society of Toxicology C3 - Antihelmintics : From discovery to resistance II, Captain’s Room: Marina Village Center: San Diego, CA- Feb. 9 - 12, 2016 T1 - Effects of monepantel on nicotinic acetylcholine receptors from Ascaris suum and Oesophagostomum dentatum SP - 11 EP - 11 UR - https://hdl.handle.net/21.15107/rcub_veterinar_3346 ER -
@conference{ author = "Trailović, Saša and Marjanović, Đorđe and Tipton, James M. and Abongwa, Melanie and Zheng, Fudan and Choudhary, Shivani and Martin, Richard J. and Robertson, Alan P.", year = "2016", abstract = "Zolvix ® is a recently introduced anthelmintic drench containing monepantel as the active ingredient. Monepantel has been demonstrated to act on deg-3/des-2 containing nAChRs in several nematodes as a positive allosteric modulator. The drug produces hypercontraction of nematode muscle. We investigated the effects of monepantel on muscle strips isolated form adult Ascaris suum. The drug did not significantly increase baseline tension when applied on its own. Contractions induced by acetylcholine and several cholininomimetic anthelmintics where antagonized by monepantel. Further investigation revealed that the antagonism was non-competitive in nature. We also investigated the effect of monepantel on nAChRs from O. dentatum heterologously expressed in Xenopus laevis oocytes. We investigated the effects of monepantel on OD3, a levamisole preferring nAChR subtype, OD4, a pyrantel preferring subtype and ACR-16 a nicotine preferring subtype. For each subtype tested monepantel applied in isolation produced no measureable currents, nor did it produce currents in the presence of choline. When monepantel was continuously applied it reduced the amplitude of acetylcholine induced currents in a concentration dependent manner for the three nAChR subtypes tested. In all three cases monepantel acted as a non-competitive antagonist on the expressed receptors. ACR-16 was particularly sensitive to monepantel inhibition. Our findings suggest that the mode of action of monepantel is more complex than previously described.", publisher = "Society of Toxicology", journal = "Antihelmintics : From discovery to resistance II, Captain’s Room: Marina Village Center: San Diego, CA- Feb. 9 - 12, 2016", title = "Effects of monepantel on nicotinic acetylcholine receptors from Ascaris suum and Oesophagostomum dentatum", pages = "11-11", url = "https://hdl.handle.net/21.15107/rcub_veterinar_3346" }
Trailović, S., Marjanović, Đ., Tipton, J. M., Abongwa, M., Zheng, F., Choudhary, S., Martin, R. J.,& Robertson, A. P.. (2016). Effects of monepantel on nicotinic acetylcholine receptors from Ascaris suum and Oesophagostomum dentatum. in Antihelmintics : From discovery to resistance II, Captain’s Room: Marina Village Center: San Diego, CA- Feb. 9 - 12, 2016 Society of Toxicology., 11-11. https://hdl.handle.net/21.15107/rcub_veterinar_3346
Trailović S, Marjanović Đ, Tipton JM, Abongwa M, Zheng F, Choudhary S, Martin RJ, Robertson AP. Effects of monepantel on nicotinic acetylcholine receptors from Ascaris suum and Oesophagostomum dentatum. in Antihelmintics : From discovery to resistance II, Captain’s Room: Marina Village Center: San Diego, CA- Feb. 9 - 12, 2016. 2016;:11-11. https://hdl.handle.net/21.15107/rcub_veterinar_3346 .
Trailović, Saša, Marjanović, Đorđe, Tipton, James M., Abongwa, Melanie, Zheng, Fudan, Choudhary, Shivani, Martin, Richard J., Robertson, Alan P., "Effects of monepantel on nicotinic acetylcholine receptors from Ascaris suum and Oesophagostomum dentatum" in Antihelmintics : From discovery to resistance II, Captain’s Room: Marina Village Center: San Diego, CA- Feb. 9 - 12, 2016 (2016):11-11, https://hdl.handle.net/21.15107/rcub_veterinar_3346 .