Pharmacology of nicotinic receptors from C. elegans muscle

Autores
Bergé, Ignacio; Dionisio, Leonardo Raul; Bouzat, Cecilia Beatriz
Año de publicación
2011
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Caenorhabditis elegans has emerged as a model organism useful for drug screening. It expresses two types of muscle nicotinic receptors (AChRs): levamisole-sensitive (L-AChR) and nicotine-sensitive (N-AChR). L-AChRs are targets of anthelmintic drugs, which act as specific and potent agonists. We here explore activation of both AChR types by the nematocide drug oxantel. Single-channel recordings from C. elegans muscle cultured cells show that oxantel elicits openings with amplitudes similar to those of L-AChRs. However, the frequency of opening is significantly reduced with respect to that observed in the presence of ACh, indicating reduced activation. In whole-cell recordings from cells expressing N-AChRs, peak currents elicited by oxantel are 45% of those elicited by ACh. Molecular docking studies show binding of oxantel to both types of AChRs, with similar binding energies but different orientations at the binding pocket. We conclude that oxantel behaves as a partial and non selective agonist of both L- and N-muscle AChRs, thus showing a different pharmacological profile compared to that of typical anthelmintic agents. These results contribute to the understanding of the pharmacology related to neuromuscular transmission in the model organism.
Fil: Bergé, Ignacio. 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: Dionisio, Leonardo Raul. 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
XXVI Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias
Huerta Grande
Argentina
Sociedad Argentina de Investigación en Neurociencias
Materia
C ELEGANS
PATCH-CLAMP
NICOTINIC RECEPTOR
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:11336/247184
Acceder
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spelling Pharmacology of nicotinic receptors from C. elegans muscleBergé, IgnacioDionisio, Leonardo RaulBouzat, Cecilia BeatrizC ELEGANSPATCH-CLAMPNICOTINIC RECEPTORhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Caenorhabditis elegans has emerged as a model organism useful for drug screening. It expresses two types of muscle nicotinic receptors (AChRs): levamisole-sensitive (L-AChR) and nicotine-sensitive (N-AChR). L-AChRs are targets of anthelmintic drugs, which act as specific and potent agonists. We here explore activation of both AChR types by the nematocide drug oxantel. Single-channel recordings from C. elegans muscle cultured cells show that oxantel elicits openings with amplitudes similar to those of L-AChRs. However, the frequency of opening is significantly reduced with respect to that observed in the presence of ACh, indicating reduced activation. In whole-cell recordings from cells expressing N-AChRs, peak currents elicited by oxantel are 45% of those elicited by ACh. Molecular docking studies show binding of oxantel to both types of AChRs, with similar binding energies but different orientations at the binding pocket. We conclude that oxantel behaves as a partial and non selective agonist of both L- and N-muscle AChRs, thus showing a different pharmacological profile compared to that of typical anthelmintic agents. These results contribute to the understanding of the pharmacology related to neuromuscular transmission in the model organism.Fil: Bergé, Ignacio. 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: Dionisio, Leonardo Raul. 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; ArgentinaXXVI Reunión Anual de la Sociedad Argentina de Investigación en NeurocienciasHuerta GrandeArgentinaSociedad Argentina de Investigación en NeurocienciasSociedad Argentina de Investigación en Neurociencia2011info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/247184Pharmacology of nicotinic receptors from C. elegans muscle; XXVI Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; Huerta Grande; Argentina; 2011; 191-191CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://saneurociencias.org.ar/wp-content/uploads/2022/01/SAN2011_Huerta-Grande_libro-de-resumenes.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:07Zoai:ri.conicet.gov.ar:11336/247184instacron: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 09:44:07.764CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Pharmacology of nicotinic receptors from C. elegans muscle
title Pharmacology of nicotinic receptors from C. elegans muscle
spellingShingle Pharmacology of nicotinic receptors from C. elegans muscle
Bergé, Ignacio
C ELEGANS
PATCH-CLAMP
NICOTINIC RECEPTOR
title_short Pharmacology of nicotinic receptors from C. elegans muscle
title_full Pharmacology of nicotinic receptors from C. elegans muscle
title_fullStr Pharmacology of nicotinic receptors from C. elegans muscle
title_full_unstemmed Pharmacology of nicotinic receptors from C. elegans muscle
title_sort Pharmacology of nicotinic receptors from C. elegans muscle
dc.creator.none.fl_str_mv Bergé, Ignacio
Dionisio, Leonardo Raul
Bouzat, Cecilia Beatriz
author Bergé, Ignacio
author_facet Bergé, Ignacio
Dionisio, Leonardo Raul
Bouzat, Cecilia Beatriz
author_role author
author2 Dionisio, Leonardo Raul
Bouzat, Cecilia Beatriz
author2_role author
author
dc.subject.none.fl_str_mv C ELEGANS
PATCH-CLAMP
NICOTINIC RECEPTOR
topic C ELEGANS
PATCH-CLAMP
NICOTINIC RECEPTOR
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 has emerged as a model organism useful for drug screening. It expresses two types of muscle nicotinic receptors (AChRs): levamisole-sensitive (L-AChR) and nicotine-sensitive (N-AChR). L-AChRs are targets of anthelmintic drugs, which act as specific and potent agonists. We here explore activation of both AChR types by the nematocide drug oxantel. Single-channel recordings from C. elegans muscle cultured cells show that oxantel elicits openings with amplitudes similar to those of L-AChRs. However, the frequency of opening is significantly reduced with respect to that observed in the presence of ACh, indicating reduced activation. In whole-cell recordings from cells expressing N-AChRs, peak currents elicited by oxantel are 45% of those elicited by ACh. Molecular docking studies show binding of oxantel to both types of AChRs, with similar binding energies but different orientations at the binding pocket. We conclude that oxantel behaves as a partial and non selective agonist of both L- and N-muscle AChRs, thus showing a different pharmacological profile compared to that of typical anthelmintic agents. These results contribute to the understanding of the pharmacology related to neuromuscular transmission in the model organism.
Fil: Bergé, Ignacio. 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: Dionisio, Leonardo Raul. 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
XXVI Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias
Huerta Grande
Argentina
Sociedad Argentina de Investigación en Neurociencias
description Caenorhabditis elegans has emerged as a model organism useful for drug screening. It expresses two types of muscle nicotinic receptors (AChRs): levamisole-sensitive (L-AChR) and nicotine-sensitive (N-AChR). L-AChRs are targets of anthelmintic drugs, which act as specific and potent agonists. We here explore activation of both AChR types by the nematocide drug oxantel. Single-channel recordings from C. elegans muscle cultured cells show that oxantel elicits openings with amplitudes similar to those of L-AChRs. However, the frequency of opening is significantly reduced with respect to that observed in the presence of ACh, indicating reduced activation. In whole-cell recordings from cells expressing N-AChRs, peak currents elicited by oxantel are 45% of those elicited by ACh. Molecular docking studies show binding of oxantel to both types of AChRs, with similar binding energies but different orientations at the binding pocket. We conclude that oxantel behaves as a partial and non selective agonist of both L- and N-muscle AChRs, thus showing a different pharmacological profile compared to that of typical anthelmintic agents. These results contribute to the understanding of the pharmacology related to neuromuscular transmission in the model organism.
publishDate 2011
dc.date.none.fl_str_mv 2011
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/11336/247184
Pharmacology of nicotinic receptors from C. elegans muscle; XXVI Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; Huerta Grande; Argentina; 2011; 191-191
CONICET Digital
CONICET
url http://hdl.handle.net/11336/247184
identifier_str_mv Pharmacology of nicotinic receptors from C. elegans muscle; XXVI Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; Huerta Grande; Argentina; 2011; 191-191
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/wp-content/uploads/2022/01/SAN2011_Huerta-Grande_libro-de-resumenes.pdf
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
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencia
publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencia
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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