Interaction of agonists of a different subtype of the nAChR and carvacrol with GABA in Ascaris suum somatic muscle contractions
Апстракт
Resistance of parasitic nematodes to anthelmintic drugs is a growing problem in human and veterinary medicine. The molecular mechanisms by which nematodes become resistant are different, but certainly one of the possible processes involves changing the drug binding site on the specific receptor. The significance of changes in individual subtypes of nicotinic acetylcholine receptors (nAChRs) for the development of resistance has not been clarified in detail. This study investigates the interaction of antinematodal drugs, agonist of different types of nAChRs and carvacrol with gamma aminobutyric acid (GABA) on the contractions of parasitic nematode A. suum. In our study, GABA (3 μM) produced significant increase of contractile EC50 value for pyrantel, and nonsignificant for bephenium and morantel, from 8.44 to 28.11 nM, 0.62 to 0.96 µM, and 3.72 to 5.69 nM, respectively. On the other hand, the maximal contractile effect (Rmax) did not change in the presence of GABA. However, when A. summ... muscle flaps were incubated with GABA 3 μM and carvacrol 100 μM, the EC50 value of pyrantel, bephenium, and morantel was increased significantly to 44.62 nM, 1.40 μM, and nonsignificantly to 7.94 nM, respectively. Furthermore, Rmax decreased by 70, 60, and 65%. Presented results indicate that the combined use of GABA receptor agonists and nicotinic receptor antagonists can effectively inhibit the neuromuscular system of nematodes, even when one of the nicotinic receptor subtypes is dysfunctional, due to the potential development of resistance.
Кључне речи:
Carvacrol / GABA / Interaction / NAChR / ResistanceИзвор:
Journal of Nematology, 2021, 53, e2021-022-Издавач:
- Exeley, Inc.
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)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200143 (Универзитет у Београду, Факултет ветеринарске медицине) (RS-MESTD-inst-2020-200143)
DOI: 10.21307/jofnem-2021-022
ISSN: 0022-300X
WoS: 000635355700001
Scopus: 2-s2.0-85103503896
Колекције
Институција/група
Fakultet veterinarske medicineTY - JOUR AU - Marjanović, Đorđe AU - Trailović, Saša M. AU - Milovanović, Mirjana PY - 2021 UR - https://vet-erinar.vet.bg.ac.rs/handle/123456789/2040 AB - Resistance of parasitic nematodes to anthelmintic drugs is a growing problem in human and veterinary medicine. The molecular mechanisms by which nematodes become resistant are different, but certainly one of the possible processes involves changing the drug binding site on the specific receptor. The significance of changes in individual subtypes of nicotinic acetylcholine receptors (nAChRs) for the development of resistance has not been clarified in detail. This study investigates the interaction of antinematodal drugs, agonist of different types of nAChRs and carvacrol with gamma aminobutyric acid (GABA) on the contractions of parasitic nematode A. suum. In our study, GABA (3 μM) produced significant increase of contractile EC50 value for pyrantel, and nonsignificant for bephenium and morantel, from 8.44 to 28.11 nM, 0.62 to 0.96 µM, and 3.72 to 5.69 nM, respectively. On the other hand, the maximal contractile effect (Rmax) did not change in the presence of GABA. However, when A. summ muscle flaps were incubated with GABA 3 μM and carvacrol 100 μM, the EC50 value of pyrantel, bephenium, and morantel was increased significantly to 44.62 nM, 1.40 μM, and nonsignificantly to 7.94 nM, respectively. Furthermore, Rmax decreased by 70, 60, and 65%. Presented results indicate that the combined use of GABA receptor agonists and nicotinic receptor antagonists can effectively inhibit the neuromuscular system of nematodes, even when one of the nicotinic receptor subtypes is dysfunctional, due to the potential development of resistance. PB - Exeley, Inc. T2 - Journal of Nematology T1 - Interaction of agonists of a different subtype of the nAChR and carvacrol with GABA in Ascaris suum somatic muscle contractions VL - 53 SP - e2021-022 DO - 10.21307/jofnem-2021-022 ER -
@article{ author = "Marjanović, Đorđe and Trailović, Saša M. and Milovanović, Mirjana", year = "2021", abstract = "Resistance of parasitic nematodes to anthelmintic drugs is a growing problem in human and veterinary medicine. The molecular mechanisms by which nematodes become resistant are different, but certainly one of the possible processes involves changing the drug binding site on the specific receptor. The significance of changes in individual subtypes of nicotinic acetylcholine receptors (nAChRs) for the development of resistance has not been clarified in detail. This study investigates the interaction of antinematodal drugs, agonist of different types of nAChRs and carvacrol with gamma aminobutyric acid (GABA) on the contractions of parasitic nematode A. suum. In our study, GABA (3 μM) produced significant increase of contractile EC50 value for pyrantel, and nonsignificant for bephenium and morantel, from 8.44 to 28.11 nM, 0.62 to 0.96 µM, and 3.72 to 5.69 nM, respectively. On the other hand, the maximal contractile effect (Rmax) did not change in the presence of GABA. However, when A. summ muscle flaps were incubated with GABA 3 μM and carvacrol 100 μM, the EC50 value of pyrantel, bephenium, and morantel was increased significantly to 44.62 nM, 1.40 μM, and nonsignificantly to 7.94 nM, respectively. Furthermore, Rmax decreased by 70, 60, and 65%. Presented results indicate that the combined use of GABA receptor agonists and nicotinic receptor antagonists can effectively inhibit the neuromuscular system of nematodes, even when one of the nicotinic receptor subtypes is dysfunctional, due to the potential development of resistance.", publisher = "Exeley, Inc.", journal = "Journal of Nematology", title = "Interaction of agonists of a different subtype of the nAChR and carvacrol with GABA in Ascaris suum somatic muscle contractions", volume = "53", pages = "e2021-022", doi = "10.21307/jofnem-2021-022" }
Marjanović, Đ., Trailović, S. M.,& Milovanović, M.. (2021). Interaction of agonists of a different subtype of the nAChR and carvacrol with GABA in Ascaris suum somatic muscle contractions. in Journal of Nematology Exeley, Inc.., 53, e2021-022. https://doi.org/10.21307/jofnem-2021-022
Marjanović Đ, Trailović SM, Milovanović M. Interaction of agonists of a different subtype of the nAChR and carvacrol with GABA in Ascaris suum somatic muscle contractions. in Journal of Nematology. 2021;53:e2021-022. doi:10.21307/jofnem-2021-022 .
Marjanović, Đorđe, Trailović, Saša M., Milovanović, Mirjana, "Interaction of agonists of a different subtype of the nAChR and carvacrol with GABA in Ascaris suum somatic muscle contractions" in Journal of Nematology, 53 (2021):e2021-022, https://doi.org/10.21307/jofnem-2021-022 . .