Cargando…
Interaction of agonists of a different subtype of the nAChR and carvacrol with GABA in Ascaris suum somatic muscle contractions
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...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Exeley Inc.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039995/ https://www.ncbi.nlm.nih.gov/pubmed/33860255 http://dx.doi.org/10.21307/jofnem-2021-022 |
_version_ | 1783677703915831296 |
---|---|
author | Marjanović, Djordje S. Trailović, Saša M. Milovanović, Mirjana |
author_facet | Marjanović, Djordje S. Trailović, Saša M. Milovanović, Mirjana |
author_sort | Marjanović, Djordje S. |
collection | PubMed |
description | 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 EC(50) 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 (R(max)) 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 EC(50) value of pyrantel, bephenium, and morantel was increased significantly to 44.62 nM, 1.40 μM, and nonsignificantly to 7.94 nM, respectively. Furthermore, R(max) 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. |
format | Online Article Text |
id | pubmed-8039995 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Exeley Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80399952021-04-14 Interaction of agonists of a different subtype of the nAChR and carvacrol with GABA in Ascaris suum somatic muscle contractions Marjanović, Djordje S. Trailović, Saša M. Milovanović, Mirjana J Nematol Arts & Humanities 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 EC(50) 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 (R(max)) 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 EC(50) value of pyrantel, bephenium, and morantel was increased significantly to 44.62 nM, 1.40 μM, and nonsignificantly to 7.94 nM, respectively. Furthermore, R(max) 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. Exeley Inc. 2021-03-26 /pmc/articles/PMC8039995/ /pubmed/33860255 http://dx.doi.org/10.21307/jofnem-2021-022 Text en © 2021 Authors https://creativecommons.org/licenses/by/4.0/This is an Open Access article licensed under the Creative Commons CC BY 4.0 license, https://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Arts & Humanities Marjanović, Djordje S. 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 |
title | Interaction of agonists of a different subtype of the nAChR and carvacrol with GABA in Ascaris suum somatic muscle contractions |
title_full | Interaction of agonists of a different subtype of the nAChR and carvacrol with GABA in Ascaris suum somatic muscle contractions |
title_fullStr | Interaction of agonists of a different subtype of the nAChR and carvacrol with GABA in Ascaris suum somatic muscle contractions |
title_full_unstemmed | Interaction of agonists of a different subtype of the nAChR and carvacrol with GABA in Ascaris suum somatic muscle contractions |
title_short | Interaction of agonists of a different subtype of the nAChR and carvacrol with GABA in Ascaris suum somatic muscle contractions |
title_sort | interaction of agonists of a different subtype of the nachr and carvacrol with gaba in ascaris suum somatic muscle contractions |
topic | Arts & Humanities |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039995/ https://www.ncbi.nlm.nih.gov/pubmed/33860255 http://dx.doi.org/10.21307/jofnem-2021-022 |
work_keys_str_mv | AT marjanovicdjordjes interactionofagonistsofadifferentsubtypeofthenachrandcarvacrolwithgabainascarissuumsomaticmusclecontractions AT trailovicsasam interactionofagonistsofadifferentsubtypeofthenachrandcarvacrolwithgabainascarissuumsomaticmusclecontractions AT milovanovicmirjana interactionofagonistsofadifferentsubtypeofthenachrandcarvacrolwithgabainascarissuumsomaticmusclecontractions |