Caenorhabditis elegans betaine-sensitive nicotinic receptors: molecular function and physiological roles.

Autores
Turani, Ornella; Hernando, Guillermina Silvana; Rodriguez Araujo, Noelia; Bouzat, Cecilia Beatriz
Año de publicación
2023
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Caenorhabditis elegans possesses an extensive and diverse family of nicotinic receptors (nAChR), many of which remained uncharacterized. nAChRs are involved in worm locomotion and are targets of anthelmintic drugs. Parasitic nematodes have acquired resistance to most anthelmintic drugs, thus generating problems in human and animal health. Because of this, the identification of novel drugs and targets is required. The potent nematocidal drug monepantel (MNP), which belongs to the recently discovered class of compounds amino-acetonitrile derivatives (AADs), has been shown to target ACR-23 nAChR. ACR-23, whose endogenous agonist is betaine (BE), is a poorly characterized nAChR present in body-wall muscle and mechanosensory neurons of nematodes. Since it is not conserved in vertebrates, ACR-23 is an interesting pharmacological target for anthelmintic drugs. Our goal is to decipher ACR-23 molecular function and its potential as a novel anthelmintic drug target. By performing locomotion assays with wild-type adult worms we showed that exogenous BE significantly increased worm motility. This effect was not observed in acr-23 mutants, indicating that the hypermotility is mediated by ACR-23. The exposure of worms to MNP paralysis and inhibited egg hatching, indicating important anthelmintic ability. Locomotion assays with mutant worms demonstrated that MNP-induced paralysis is mediated by ACR-23 and DEG-3/DES-2, a nAChR present in sensory neurons involved in nociception and chemotaxis. By patch-clamp recordings from cultured C. elegans L1 muscle cells, we described for the first time the properties of BE-elicited single-channel and macroscopic currents. Our study provides novel information aiming at the elucidation of the molecular function and pharmacology of the nAChR family. It also contributes to the understanding of the molecular basis of anthelmintic action, which paves the way for the development of novel drugs. produced the opposite effect, resulting in reduced motility as a function of concentration (EC50 = 50 µM). MNP induced spastic
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: Rodriguez Araujo, Noelia. 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
24th International C. elegans Conference
Glasgow
Escocia
Genetics Society of America
Materia
CAENORHABDITIS ELEGANS
CYS-LOOP RECEPTORS
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:11336/224481
Acceder
id CONICETDig_3bd857f7262dea7f42fe3e639d306022
oai_identifier_str oai:ri.conicet.gov.ar:11336/224481
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Caenorhabditis elegans betaine-sensitive nicotinic receptors: molecular function and physiological roles.Turani, OrnellaHernando, Guillermina SilvanaRodriguez Araujo, NoeliaBouzat, Cecilia BeatrizCAENORHABDITIS ELEGANSCYS-LOOP RECEPTORSANTHELMINTICShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Caenorhabditis elegans possesses an extensive and diverse family of nicotinic receptors (nAChR), many of which remained uncharacterized. nAChRs are involved in worm locomotion and are targets of anthelmintic drugs. Parasitic nematodes have acquired resistance to most anthelmintic drugs, thus generating problems in human and animal health. Because of this, the identification of novel drugs and targets is required. The potent nematocidal drug monepantel (MNP), which belongs to the recently discovered class of compounds amino-acetonitrile derivatives (AADs), has been shown to target ACR-23 nAChR. ACR-23, whose endogenous agonist is betaine (BE), is a poorly characterized nAChR present in body-wall muscle and mechanosensory neurons of nematodes. Since it is not conserved in vertebrates, ACR-23 is an interesting pharmacological target for anthelmintic drugs. Our goal is to decipher ACR-23 molecular function and its potential as a novel anthelmintic drug target. By performing locomotion assays with wild-type adult worms we showed that exogenous BE significantly increased worm motility. This effect was not observed in acr-23 mutants, indicating that the hypermotility is mediated by ACR-23. The exposure of worms to MNP paralysis and inhibited egg hatching, indicating important anthelmintic ability. Locomotion assays with mutant worms demonstrated that MNP-induced paralysis is mediated by ACR-23 and DEG-3/DES-2, a nAChR present in sensory neurons involved in nociception and chemotaxis. By patch-clamp recordings from cultured C. elegans L1 muscle cells, we described for the first time the properties of BE-elicited single-channel and macroscopic currents. Our study provides novel information aiming at the elucidation of the molecular function and pharmacology of the nAChR family. It also contributes to the understanding of the molecular basis of anthelmintic action, which paves the way for the development of novel drugs. produced the opposite effect, resulting in reduced motility as a function of concentration (EC50 = 50 µM). MNP induced spasticFil: 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: Rodriguez Araujo, Noelia. 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; Argentina24th International C. elegans ConferenceGlasgowEscociaGenetics Society of AmericaGenetics Society of America2023info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectConferenciaBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/224481Caenorhabditis elegans betaine-sensitive nicotinic receptors: molecular function and physiological roles.; 24th International C. elegans Conference; Glasgow; Escocia; 2023; 377-378CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://genetics-gsa.org/celegans2023/program-and-abstract-books/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 Técnicas2025-09-29T10:32:01Zoai:ri.conicet.gov.ar:11336/224481instacron: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:34982025-09-29 10:32:01.687CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Caenorhabditis elegans betaine-sensitive nicotinic receptors: molecular function and physiological roles.
title Caenorhabditis elegans betaine-sensitive nicotinic receptors: molecular function and physiological roles.
spellingShingle Caenorhabditis elegans betaine-sensitive nicotinic receptors: molecular function and physiological roles.
Turani, Ornella
CAENORHABDITIS ELEGANS
CYS-LOOP RECEPTORS
ANTHELMINTICS
title_short Caenorhabditis elegans betaine-sensitive nicotinic receptors: molecular function and physiological roles.
title_full Caenorhabditis elegans betaine-sensitive nicotinic receptors: molecular function and physiological roles.
title_fullStr Caenorhabditis elegans betaine-sensitive nicotinic receptors: molecular function and physiological roles.
title_full_unstemmed Caenorhabditis elegans betaine-sensitive nicotinic receptors: molecular function and physiological roles.
title_sort Caenorhabditis elegans betaine-sensitive nicotinic receptors: molecular function and physiological roles.
dc.creator.none.fl_str_mv Turani, Ornella
Hernando, Guillermina Silvana
Rodriguez Araujo, Noelia
Bouzat, Cecilia Beatriz
author Turani, Ornella
author_facet Turani, Ornella
Hernando, Guillermina Silvana
Rodriguez Araujo, Noelia
Bouzat, Cecilia Beatriz
author_role author
author2 Hernando, Guillermina Silvana
Rodriguez Araujo, Noelia
Bouzat, Cecilia Beatriz
author2_role author
author
author
dc.subject.none.fl_str_mv CAENORHABDITIS ELEGANS
CYS-LOOP RECEPTORS
ANTHELMINTICS
topic CAENORHABDITIS ELEGANS
CYS-LOOP RECEPTORS
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 Caenorhabditis elegans possesses an extensive and diverse family of nicotinic receptors (nAChR), many of which remained uncharacterized. nAChRs are involved in worm locomotion and are targets of anthelmintic drugs. Parasitic nematodes have acquired resistance to most anthelmintic drugs, thus generating problems in human and animal health. Because of this, the identification of novel drugs and targets is required. The potent nematocidal drug monepantel (MNP), which belongs to the recently discovered class of compounds amino-acetonitrile derivatives (AADs), has been shown to target ACR-23 nAChR. ACR-23, whose endogenous agonist is betaine (BE), is a poorly characterized nAChR present in body-wall muscle and mechanosensory neurons of nematodes. Since it is not conserved in vertebrates, ACR-23 is an interesting pharmacological target for anthelmintic drugs. Our goal is to decipher ACR-23 molecular function and its potential as a novel anthelmintic drug target. By performing locomotion assays with wild-type adult worms we showed that exogenous BE significantly increased worm motility. This effect was not observed in acr-23 mutants, indicating that the hypermotility is mediated by ACR-23. The exposure of worms to MNP paralysis and inhibited egg hatching, indicating important anthelmintic ability. Locomotion assays with mutant worms demonstrated that MNP-induced paralysis is mediated by ACR-23 and DEG-3/DES-2, a nAChR present in sensory neurons involved in nociception and chemotaxis. By patch-clamp recordings from cultured C. elegans L1 muscle cells, we described for the first time the properties of BE-elicited single-channel and macroscopic currents. Our study provides novel information aiming at the elucidation of the molecular function and pharmacology of the nAChR family. It also contributes to the understanding of the molecular basis of anthelmintic action, which paves the way for the development of novel drugs. produced the opposite effect, resulting in reduced motility as a function of concentration (EC50 = 50 µM). MNP induced spastic
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: Rodriguez Araujo, Noelia. 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
24th International C. elegans Conference
Glasgow
Escocia
Genetics Society of America
description Caenorhabditis elegans possesses an extensive and diverse family of nicotinic receptors (nAChR), many of which remained uncharacterized. nAChRs are involved in worm locomotion and are targets of anthelmintic drugs. Parasitic nematodes have acquired resistance to most anthelmintic drugs, thus generating problems in human and animal health. Because of this, the identification of novel drugs and targets is required. The potent nematocidal drug monepantel (MNP), which belongs to the recently discovered class of compounds amino-acetonitrile derivatives (AADs), has been shown to target ACR-23 nAChR. ACR-23, whose endogenous agonist is betaine (BE), is a poorly characterized nAChR present in body-wall muscle and mechanosensory neurons of nematodes. Since it is not conserved in vertebrates, ACR-23 is an interesting pharmacological target for anthelmintic drugs. Our goal is to decipher ACR-23 molecular function and its potential as a novel anthelmintic drug target. By performing locomotion assays with wild-type adult worms we showed that exogenous BE significantly increased worm motility. This effect was not observed in acr-23 mutants, indicating that the hypermotility is mediated by ACR-23. The exposure of worms to MNP paralysis and inhibited egg hatching, indicating important anthelmintic ability. Locomotion assays with mutant worms demonstrated that MNP-induced paralysis is mediated by ACR-23 and DEG-3/DES-2, a nAChR present in sensory neurons involved in nociception and chemotaxis. By patch-clamp recordings from cultured C. elegans L1 muscle cells, we described for the first time the properties of BE-elicited single-channel and macroscopic currents. Our study provides novel information aiming at the elucidation of the molecular function and pharmacology of the nAChR family. It also contributes to the understanding of the molecular basis of anthelmintic action, which paves the way for the development of novel drugs. produced the opposite effect, resulting in reduced motility as a function of concentration (EC50 = 50 µM). MNP induced spastic
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Conferencia
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/11336/224481
Caenorhabditis elegans betaine-sensitive nicotinic receptors: molecular function and physiological roles.; 24th International C. elegans Conference; Glasgow; Escocia; 2023; 377-378
CONICET Digital
CONICET
url http://hdl.handle.net/11336/224481
identifier_str_mv Caenorhabditis elegans betaine-sensitive nicotinic receptors: molecular function and physiological roles.; 24th International C. elegans Conference; Glasgow; Escocia; 2023; 377-378
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://genetics-gsa.org/celegans2023/program-and-abstract-books/
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 Genetics Society of America
publisher.none.fl_str_mv Genetics Society of America
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
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score 13.260194

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