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dc.contributor.author
Turani, Ornella
dc.contributor.author
Hernando, Guillermina Silvana
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Rodriguez Araujo, Noelia
dc.contributor.author
Bouzat, Cecilia Beatriz
dc.date.available
2024-01-22T15:16:30Z
dc.date.issued
2023
dc.identifier.citation
Caenorhabditis elegans betaine-sensitive nicotinic receptors: molecular function and physiological roles.; 24th International C. elegans Conference; Glasgow; Escocia; 2023; 377-378
dc.identifier.uri
http://hdl.handle.net/11336/224481
dc.description.abstract
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
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Genetics Society of America
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
CAENORHABDITIS ELEGANS
dc.subject
CYS-LOOP RECEPTORS
dc.subject
ANTHELMINTICS
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Bioquímica y Biología Molecular
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Caenorhabditis elegans betaine-sensitive nicotinic receptors: molecular function and physiological roles.
dc.type
info:eu-repo/semantics/publishedVersion
dc.type
info:eu-repo/semantics/conferenceObject
dc.type
info:ar-repo/semantics/documento de conferencia
dc.date.updated
2024-01-16T14:00:45Z
dc.journal.pagination
377-378
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Rockville
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://genetics-gsa.org/celegans2023/program-and-abstract-books/
dc.conicet.rol
Autor
dc.conicet.rol
Autor
dc.conicet.rol
Autor
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Autor
dc.coverage
Internacional
dc.type.subtype
Conferencia
dc.description.nombreEvento
24th International C. elegans Conference
dc.date.evento
2023-06-24
dc.description.ciudadEvento
Glasgow
dc.description.paisEvento
Escocia
dc.type.publicacion
Book
dc.description.institucionOrganizadora
Genetics Society of America
dc.source.libro
24th International C. elegans Conference
dc.date.eventoHasta
2013-06-28
dc.type
Conferencia
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