GABA receptors of Caenorhabditis elegans muscle as targets of anthelmintic agents

Autores
Hernando, Guillermina Silvana; Bouzat, Cecilia Beatriz
Año de publicación
2012
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Gamma-aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in vertebrates and invertebrates. GABA receptors are targets of anxiolytic and antiepileptic drugs as well as of insecticides and anthelmintics. In nematodes, GABARs are present in the muscle and the appropriate balance of acetylcholine and GABA signaling is required for coordinated contraction and movement. We studied muscle GABARs from C. elegans to characterize and evaluate at both the molecular and behavioral levels the mode of action of GABAergic agonists and anthelmintics. Single-channel currents of ~2.5 pA from GABARs activated by GABA, muscimol and piperazine can be detected from cell-attached patches in muscle cells. Macroscopic current recordings show full desensitization of GABARs in the presence of the three agonists and indicate that piperazine is less efficacious than GABA. Behavioral assays show that piperazine produces flaccid paralysis and that its effect is potentiated by ivermectin, a positive allosteric modulator of GABARs. Our results also show differential sensitivity to these drugs between adult and larval stages. The lack of GABARs in vertebrate muscle highlights the importance of their characterization in nematodes, not only from an evolutionary point of view but also for the development of more selective anthelmintic therapies
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
XXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias
Huerta Grande
Argentina
Sociedad Argentina de Investigación en Neurociencias
Materia
C ELEGANS
GABAA RECEPTORS
ANTIHELMINTIC
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:11336/235876
Acceder
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network_name_str CONICET Digital (CONICET)
spelling GABA receptors of Caenorhabditis elegans muscle as targets of anthelmintic agentsHernando, Guillermina SilvanaBouzat, Cecilia BeatrizC ELEGANSGABAA RECEPTORSANTIHELMINTIChttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Gamma-aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in vertebrates and invertebrates. GABA receptors are targets of anxiolytic and antiepileptic drugs as well as of insecticides and anthelmintics. In nematodes, GABARs are present in the muscle and the appropriate balance of acetylcholine and GABA signaling is required for coordinated contraction and movement. We studied muscle GABARs from C. elegans to characterize and evaluate at both the molecular and behavioral levels the mode of action of GABAergic agonists and anthelmintics. Single-channel currents of ~2.5 pA from GABARs activated by GABA, muscimol and piperazine can be detected from cell-attached patches in muscle cells. Macroscopic current recordings show full desensitization of GABARs in the presence of the three agonists and indicate that piperazine is less efficacious than GABA. Behavioral assays show that piperazine produces flaccid paralysis and that its effect is potentiated by ivermectin, a positive allosteric modulator of GABARs. Our results also show differential sensitivity to these drugs between adult and larval stages. The lack of GABARs in vertebrate muscle highlights the importance of their characterization in nematodes, not only from an evolutionary point of view but also for the development of more selective anthelmintic therapiesFil: 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; ArgentinaXXVII Congreso Anual de la Sociedad Argentina de Investigación en NeurocienciasHuerta GrandeArgentinaSociedad Argentina de Investigación en NeurocienciasSociedad Argentina de Investigación en Neurociencias2012info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/mswordapplication/pdfhttp://hdl.handle.net/11336/235876GABA receptors of Caenorhabditis elegans muscle as targets of anthelmintic agents; XXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; Huerta Grande; Argentina; 2012; 221-221CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://saneurociencias.org.ar/congresos-san-2/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:35:34Zoai:ri.conicet.gov.ar:11336/235876instacron: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:34982025-10-15 14:35:34.792CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv GABA receptors of Caenorhabditis elegans muscle as targets of anthelmintic agents
title GABA receptors of Caenorhabditis elegans muscle as targets of anthelmintic agents
spellingShingle GABA receptors of Caenorhabditis elegans muscle as targets of anthelmintic agents
Hernando, Guillermina Silvana
C ELEGANS
GABAA RECEPTORS
ANTIHELMINTIC
title_short GABA receptors of Caenorhabditis elegans muscle as targets of anthelmintic agents
title_full GABA receptors of Caenorhabditis elegans muscle as targets of anthelmintic agents
title_fullStr GABA receptors of Caenorhabditis elegans muscle as targets of anthelmintic agents
title_full_unstemmed GABA receptors of Caenorhabditis elegans muscle as targets of anthelmintic agents
title_sort GABA receptors of Caenorhabditis elegans muscle as targets of anthelmintic agents
dc.creator.none.fl_str_mv Hernando, Guillermina Silvana
Bouzat, Cecilia Beatriz
author Hernando, Guillermina Silvana
author_facet Hernando, Guillermina Silvana
Bouzat, Cecilia Beatriz
author_role author
author2 Bouzat, Cecilia Beatriz
author2_role author
dc.subject.none.fl_str_mv C ELEGANS
GABAA RECEPTORS
ANTIHELMINTIC
topic C ELEGANS
GABAA RECEPTORS
ANTIHELMINTIC
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Gamma-aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in vertebrates and invertebrates. GABA receptors are targets of anxiolytic and antiepileptic drugs as well as of insecticides and anthelmintics. In nematodes, GABARs are present in the muscle and the appropriate balance of acetylcholine and GABA signaling is required for coordinated contraction and movement. We studied muscle GABARs from C. elegans to characterize and evaluate at both the molecular and behavioral levels the mode of action of GABAergic agonists and anthelmintics. Single-channel currents of ~2.5 pA from GABARs activated by GABA, muscimol and piperazine can be detected from cell-attached patches in muscle cells. Macroscopic current recordings show full desensitization of GABARs in the presence of the three agonists and indicate that piperazine is less efficacious than GABA. Behavioral assays show that piperazine produces flaccid paralysis and that its effect is potentiated by ivermectin, a positive allosteric modulator of GABARs. Our results also show differential sensitivity to these drugs between adult and larval stages. The lack of GABARs in vertebrate muscle highlights the importance of their characterization in nematodes, not only from an evolutionary point of view but also for the development of more selective anthelmintic therapies
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
XXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias
Huerta Grande
Argentina
Sociedad Argentina de Investigación en Neurociencias
description Gamma-aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in vertebrates and invertebrates. GABA receptors are targets of anxiolytic and antiepileptic drugs as well as of insecticides and anthelmintics. In nematodes, GABARs are present in the muscle and the appropriate balance of acetylcholine and GABA signaling is required for coordinated contraction and movement. We studied muscle GABARs from C. elegans to characterize and evaluate at both the molecular and behavioral levels the mode of action of GABAergic agonists and anthelmintics. Single-channel currents of ~2.5 pA from GABARs activated by GABA, muscimol and piperazine can be detected from cell-attached patches in muscle cells. Macroscopic current recordings show full desensitization of GABARs in the presence of the three agonists and indicate that piperazine is less efficacious than GABA. Behavioral assays show that piperazine produces flaccid paralysis and that its effect is potentiated by ivermectin, a positive allosteric modulator of GABARs. Our results also show differential sensitivity to these drugs between adult and larval stages. The lack of GABARs in vertebrate muscle highlights the importance of their characterization in nematodes, not only from an evolutionary point of view but also for the development of more selective anthelmintic therapies
publishDate 2012
dc.date.none.fl_str_mv 2012
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
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/11336/235876
GABA receptors of Caenorhabditis elegans muscle as targets of anthelmintic agents; XXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; Huerta Grande; Argentina; 2012; 221-221
CONICET Digital
CONICET
url http://hdl.handle.net/11336/235876
identifier_str_mv GABA receptors of Caenorhabditis elegans muscle as targets of anthelmintic agents; XXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; Huerta Grande; Argentina; 2012; 221-221
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://saneurociencias.org.ar/congresos-san-2/
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/msword
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencias
publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencias
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 13.22299

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