Characterization of the antiparasitic bephenium as an agonist of Caenorhabditis elegans levamisole-sensitive nicotinic receptors

Autores
Turani, Ornella; Hernando, Guillermina Silvana; Bouzat, Cecilia Beatriz
Año de publicación
2017
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that mediate fast synaptic transmission and are involved in neuromuscular transmission. Nematode muscle nAChRs are of clinical importance because they are targets of anthelmintic drugs. The muscle nAChRs of nematode parasites fall into three pharmacological classes that are preferentially activated by levamisole (L-type), nicotine (N-type) and bephenium (B-type). Caenorhabditis elegans muscle contains the N-AChR and L-AChR types. We therefore sought to explore the action of bephenium at C. elegans. Behavioral studies reveal that wild type worms are sensitive to bephenium. The drug causes spastic paralysis but with less potency than levamisole. Thelev-8and unc-38 null mutant strains, which lack accessory (LEV-8) and essential (UNC-38) subunits of L- AChRs, show partial and full resistance to bephenium,respectively. To determine the mechanism of action of bephenium we used a primary culture system that allows differentiation of embryonic cells into L1 larva muscle cells in vitro. Our results reveal that bephenium (1-100 µM) activates a single population of ~3.6 pA amplitude channels (-100 mV) that correspond to the L-AChR channels. The open-channel lifetime is similar to that of ACh-activated channels (~0.2 ms). Because in parasites the receptor target of bephenium contains the ACR-8 subunit, and in C. elegans ACR-8 is a candidate subunit to replace LEV8,we also evaluated the action of this drug in the lev-8 null mutant strain. We found that bephenium also activates L-AChRs lacking LEV-8, although the activity pattern differs from that of wild-type L-AChRs. Overall, we characterized the agonistic action of bephenium, which is used for parasitic infections caused by intestinal helminths, at the C. elegans L-AChR
Fil: Turani, Ornella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Hernando, Guillermina Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
First Latin American Worm Meeting
Montevideo
Uruguay
Institut Pasteur de Montevideo
Materia
C.ELEGANS
BEPHENIUM
ANTHELMINTICS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/230177
Acceder
id CONICETDig_4fac0d8bef6b4d1b210eadf14ed9d9f5
oai_identifier_str oai:ri.conicet.gov.ar:11336/230177
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Characterization of the antiparasitic bephenium as an agonist of Caenorhabditis elegans levamisole-sensitive nicotinic receptorsTurani, OrnellaHernando, Guillermina SilvanaBouzat, Cecilia BeatrizC.ELEGANSBEPHENIUMANTHELMINTICShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that mediate fast synaptic transmission and are involved in neuromuscular transmission. Nematode muscle nAChRs are of clinical importance because they are targets of anthelmintic drugs. The muscle nAChRs of nematode parasites fall into three pharmacological classes that are preferentially activated by levamisole (L-type), nicotine (N-type) and bephenium (B-type). Caenorhabditis elegans muscle contains the N-AChR and L-AChR types. We therefore sought to explore the action of bephenium at C. elegans. Behavioral studies reveal that wild type worms are sensitive to bephenium. The drug causes spastic paralysis but with less potency than levamisole. Thelev-8and unc-38 null mutant strains, which lack accessory (LEV-8) and essential (UNC-38) subunits of L- AChRs, show partial and full resistance to bephenium,respectively. To determine the mechanism of action of bephenium we used a primary culture system that allows differentiation of embryonic cells into L1 larva muscle cells in vitro. Our results reveal that bephenium (1-100 µM) activates a single population of ~3.6 pA amplitude channels (-100 mV) that correspond to the L-AChR channels. The open-channel lifetime is similar to that of ACh-activated channels (~0.2 ms). Because in parasites the receptor target of bephenium contains the ACR-8 subunit, and in C. elegans ACR-8 is a candidate subunit to replace LEV8,we also evaluated the action of this drug in the lev-8 null mutant strain. We found that bephenium also activates L-AChRs lacking LEV-8, although the activity pattern differs from that of wild-type L-AChRs. Overall, we characterized the agonistic action of bephenium, which is used for parasitic infections caused by intestinal helminths, at the C. elegans L-AChRFil: Turani, Ornella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Hernando, Guillermina Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFirst Latin American Worm MeetingMontevideoUruguayInstitut Pasteur de MontevideoInstitut Pasteur de Montevideo2017info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectSimposioBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/230177Characterization of the antiparasitic bephenium as an agonist of Caenorhabditis elegans levamisole-sensitive nicotinic receptors; First Latin American Worm Meeting; Montevideo; Uruguay; 2017; 42-42CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://gusaneros.com/swms/Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:04:04Zoai:ri.conicet.gov.ar:11336/230177instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:04:05.127CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Characterization of the antiparasitic bephenium as an agonist of Caenorhabditis elegans levamisole-sensitive nicotinic receptors
title Characterization of the antiparasitic bephenium as an agonist of Caenorhabditis elegans levamisole-sensitive nicotinic receptors
spellingShingle Characterization of the antiparasitic bephenium as an agonist of Caenorhabditis elegans levamisole-sensitive nicotinic receptors
Turani, Ornella
C.ELEGANS
BEPHENIUM
ANTHELMINTICS
title_short Characterization of the antiparasitic bephenium as an agonist of Caenorhabditis elegans levamisole-sensitive nicotinic receptors
title_full Characterization of the antiparasitic bephenium as an agonist of Caenorhabditis elegans levamisole-sensitive nicotinic receptors
title_fullStr Characterization of the antiparasitic bephenium as an agonist of Caenorhabditis elegans levamisole-sensitive nicotinic receptors
title_full_unstemmed Characterization of the antiparasitic bephenium as an agonist of Caenorhabditis elegans levamisole-sensitive nicotinic receptors
title_sort Characterization of the antiparasitic bephenium as an agonist of Caenorhabditis elegans levamisole-sensitive nicotinic receptors
dc.creator.none.fl_str_mv Turani, Ornella
Hernando, Guillermina Silvana
Bouzat, Cecilia Beatriz
author Turani, Ornella
author_facet Turani, Ornella
Hernando, Guillermina Silvana
Bouzat, Cecilia Beatriz
author_role author
author2 Hernando, Guillermina Silvana
Bouzat, Cecilia Beatriz
author2_role author
author
dc.subject.none.fl_str_mv C.ELEGANS
BEPHENIUM
ANTHELMINTICS
topic C.ELEGANS
BEPHENIUM
ANTHELMINTICS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that mediate fast synaptic transmission and are involved in neuromuscular transmission. Nematode muscle nAChRs are of clinical importance because they are targets of anthelmintic drugs. The muscle nAChRs of nematode parasites fall into three pharmacological classes that are preferentially activated by levamisole (L-type), nicotine (N-type) and bephenium (B-type). Caenorhabditis elegans muscle contains the N-AChR and L-AChR types. We therefore sought to explore the action of bephenium at C. elegans. Behavioral studies reveal that wild type worms are sensitive to bephenium. The drug causes spastic paralysis but with less potency than levamisole. Thelev-8and unc-38 null mutant strains, which lack accessory (LEV-8) and essential (UNC-38) subunits of L- AChRs, show partial and full resistance to bephenium,respectively. To determine the mechanism of action of bephenium we used a primary culture system that allows differentiation of embryonic cells into L1 larva muscle cells in vitro. Our results reveal that bephenium (1-100 µM) activates a single population of ~3.6 pA amplitude channels (-100 mV) that correspond to the L-AChR channels. The open-channel lifetime is similar to that of ACh-activated channels (~0.2 ms). Because in parasites the receptor target of bephenium contains the ACR-8 subunit, and in C. elegans ACR-8 is a candidate subunit to replace LEV8,we also evaluated the action of this drug in the lev-8 null mutant strain. We found that bephenium also activates L-AChRs lacking LEV-8, although the activity pattern differs from that of wild-type L-AChRs. Overall, we characterized the agonistic action of bephenium, which is used for parasitic infections caused by intestinal helminths, at the C. elegans L-AChR
Fil: Turani, Ornella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Hernando, Guillermina Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
First Latin American Worm Meeting
Montevideo
Uruguay
Institut Pasteur de Montevideo
description Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that mediate fast synaptic transmission and are involved in neuromuscular transmission. Nematode muscle nAChRs are of clinical importance because they are targets of anthelmintic drugs. The muscle nAChRs of nematode parasites fall into three pharmacological classes that are preferentially activated by levamisole (L-type), nicotine (N-type) and bephenium (B-type). Caenorhabditis elegans muscle contains the N-AChR and L-AChR types. We therefore sought to explore the action of bephenium at C. elegans. Behavioral studies reveal that wild type worms are sensitive to bephenium. The drug causes spastic paralysis but with less potency than levamisole. Thelev-8and unc-38 null mutant strains, which lack accessory (LEV-8) and essential (UNC-38) subunits of L- AChRs, show partial and full resistance to bephenium,respectively. To determine the mechanism of action of bephenium we used a primary culture system that allows differentiation of embryonic cells into L1 larva muscle cells in vitro. Our results reveal that bephenium (1-100 µM) activates a single population of ~3.6 pA amplitude channels (-100 mV) that correspond to the L-AChR channels. The open-channel lifetime is similar to that of ACh-activated channels (~0.2 ms). Because in parasites the receptor target of bephenium contains the ACR-8 subunit, and in C. elegans ACR-8 is a candidate subunit to replace LEV8,we also evaluated the action of this drug in the lev-8 null mutant strain. We found that bephenium also activates L-AChRs lacking LEV-8, although the activity pattern differs from that of wild-type L-AChRs. Overall, we characterized the agonistic action of bephenium, which is used for parasitic infections caused by intestinal helminths, at the C. elegans L-AChR
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Simposio
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/230177
Characterization of the antiparasitic bephenium as an agonist of Caenorhabditis elegans levamisole-sensitive nicotinic receptors; First Latin American Worm Meeting; Montevideo; Uruguay; 2017; 42-42
CONICET Digital
CONICET
url http://hdl.handle.net/11336/230177
identifier_str_mv Characterization of the antiparasitic bephenium as an agonist of Caenorhabditis elegans levamisole-sensitive nicotinic receptors; First Latin American Worm Meeting; Montevideo; Uruguay; 2017; 42-42
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://gusaneros.com/swms/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Institut Pasteur de Montevideo
publisher.none.fl_str_mv Institut Pasteur de Montevideo
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269836280856576
score 12.885934

Publicaciones similares