Activation and modulation of the caenorhabditis elegans serotonin-gated chloride channel

Autores
Rodriguez Araujo, Noelia; Corradi, Jeremias; Bouzat, Cecilia Beatriz
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Serotonin-gated ion channels (5-HT3) belong to the family of Cys-loop receptors, which are pentameric proteins that mediate fast synaptic transmission. In mammals, 5- HT3 are non-selective cationic channels that can be found as homomers (5-HT3A) or heteromers. The free-leaving nematode Caenorhabditis elegans is a model for the study of the nervous system and for antiparasitic drug discovery. As parasitic nematodes, C. elegans contains a homomeric serotonin-gated chloride channel, MOD-1, that modulates locomotory behavior. The absence of this receptor in vertebrates, converts MOD-1 into a potential antiparasitic drug target. We expressed MOD-1 in mammalian cells and explored by patch-clamp recordings its activation and modulation properties. Dose-response curves revealed an EC50 for 5-HT activation of about 1 µM, which is in the same range as that of human 5-HT3A receptors. The analysis of whole-cell currents determined that MOD-1 channels do not show rectification, desensitize slowly in the presence of 5-HT, and recover from desensitization with a time constant of about 1 s. In contrast to their actions at mammalian 5-HT3 receptors, 5- hydroxyindol and thymol do not potentiate MOD-1 currents. The antiparasitic drug ivermectin (IVM), which acts as activator or potentiator of different Cys-loop receptors, neither activates nor potentiates MOD-1 but pre-exposure to IVM inhibits MOD-1 currents. To gain further insights into the molecular function of the native MOD-1, we sought to identify serotonin-activated chloride channels from C. elegans neurons expressing MOD-1 and compared to MOD-1 channels heterologously expressed in mammalian cells. The understanding of the molecular pharmacology of MOD-1 contributes to our knowledge of the Cys-loop receptor family and to its potential as a novel drug target for anthelmintic therapy.
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: Corradi, Jeremias. 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
LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Buenos Aires
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
The Histochemical Society
Materia
caenorhabditis elegans
SEROTONIN
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:11336/163975
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Activation and modulation of the caenorhabditis elegans serotonin-gated chloride channelRodriguez Araujo, NoeliaCorradi, JeremiasBouzat, Cecilia Beatrizcaenorhabditis elegansSEROTONINhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Serotonin-gated ion channels (5-HT3) belong to the family of Cys-loop receptors, which are pentameric proteins that mediate fast synaptic transmission. In mammals, 5- HT3 are non-selective cationic channels that can be found as homomers (5-HT3A) or heteromers. The free-leaving nematode Caenorhabditis elegans is a model for the study of the nervous system and for antiparasitic drug discovery. As parasitic nematodes, C. elegans contains a homomeric serotonin-gated chloride channel, MOD-1, that modulates locomotory behavior. The absence of this receptor in vertebrates, converts MOD-1 into a potential antiparasitic drug target. We expressed MOD-1 in mammalian cells and explored by patch-clamp recordings its activation and modulation properties. Dose-response curves revealed an EC50 for 5-HT activation of about 1 µM, which is in the same range as that of human 5-HT3A receptors. The analysis of whole-cell currents determined that MOD-1 channels do not show rectification, desensitize slowly in the presence of 5-HT, and recover from desensitization with a time constant of about 1 s. In contrast to their actions at mammalian 5-HT3 receptors, 5- hydroxyindol and thymol do not potentiate MOD-1 currents. The antiparasitic drug ivermectin (IVM), which acts as activator or potentiator of different Cys-loop receptors, neither activates nor potentiates MOD-1 but pre-exposure to IVM inhibits MOD-1 currents. To gain further insights into the molecular function of the native MOD-1, we sought to identify serotonin-activated chloride channels from C. elegans neurons expressing MOD-1 and compared to MOD-1 channels heterologously expressed in mammalian cells. The understanding of the molecular pharmacology of MOD-1 contributes to our knowledge of the Cys-loop receptor family and to its potential as a novel drug target for anthelmintic therapy.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; ArgentinaFil: Corradi, Jeremias. 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; ArgentinaLXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioBuenos AiresArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioThe Histochemical SocietyFundación Revista Medicina2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/163975Activation and modulation of the caenorhabditis elegans serotonin-gated chloride channel; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Buenos Aires; Argentina; 2019; 207-2070025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicinaNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:59:39Zoai:ri.conicet.gov.ar:11336/163975instacron: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 09:59:39.563CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Activation and modulation of the caenorhabditis elegans serotonin-gated chloride channel
title Activation and modulation of the caenorhabditis elegans serotonin-gated chloride channel
spellingShingle Activation and modulation of the caenorhabditis elegans serotonin-gated chloride channel
Rodriguez Araujo, Noelia
caenorhabditis elegans
SEROTONIN
title_short Activation and modulation of the caenorhabditis elegans serotonin-gated chloride channel
title_full Activation and modulation of the caenorhabditis elegans serotonin-gated chloride channel
title_fullStr Activation and modulation of the caenorhabditis elegans serotonin-gated chloride channel
title_full_unstemmed Activation and modulation of the caenorhabditis elegans serotonin-gated chloride channel
title_sort Activation and modulation of the caenorhabditis elegans serotonin-gated chloride channel
dc.creator.none.fl_str_mv Rodriguez Araujo, Noelia
Corradi, Jeremias
Bouzat, Cecilia Beatriz
author Rodriguez Araujo, Noelia
author_facet Rodriguez Araujo, Noelia
Corradi, Jeremias
Bouzat, Cecilia Beatriz
author_role author
author2 Corradi, Jeremias
Bouzat, Cecilia Beatriz
author2_role author
author
dc.subject.none.fl_str_mv caenorhabditis elegans
SEROTONIN
topic caenorhabditis elegans
SEROTONIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Serotonin-gated ion channels (5-HT3) belong to the family of Cys-loop receptors, which are pentameric proteins that mediate fast synaptic transmission. In mammals, 5- HT3 are non-selective cationic channels that can be found as homomers (5-HT3A) or heteromers. The free-leaving nematode Caenorhabditis elegans is a model for the study of the nervous system and for antiparasitic drug discovery. As parasitic nematodes, C. elegans contains a homomeric serotonin-gated chloride channel, MOD-1, that modulates locomotory behavior. The absence of this receptor in vertebrates, converts MOD-1 into a potential antiparasitic drug target. We expressed MOD-1 in mammalian cells and explored by patch-clamp recordings its activation and modulation properties. Dose-response curves revealed an EC50 for 5-HT activation of about 1 µM, which is in the same range as that of human 5-HT3A receptors. The analysis of whole-cell currents determined that MOD-1 channels do not show rectification, desensitize slowly in the presence of 5-HT, and recover from desensitization with a time constant of about 1 s. In contrast to their actions at mammalian 5-HT3 receptors, 5- hydroxyindol and thymol do not potentiate MOD-1 currents. The antiparasitic drug ivermectin (IVM), which acts as activator or potentiator of different Cys-loop receptors, neither activates nor potentiates MOD-1 but pre-exposure to IVM inhibits MOD-1 currents. To gain further insights into the molecular function of the native MOD-1, we sought to identify serotonin-activated chloride channels from C. elegans neurons expressing MOD-1 and compared to MOD-1 channels heterologously expressed in mammalian cells. The understanding of the molecular pharmacology of MOD-1 contributes to our knowledge of the Cys-loop receptor family and to its potential as a novel drug target for anthelmintic therapy.
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: Corradi, Jeremias. 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
LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Buenos Aires
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
The Histochemical Society
description Serotonin-gated ion channels (5-HT3) belong to the family of Cys-loop receptors, which are pentameric proteins that mediate fast synaptic transmission. In mammals, 5- HT3 are non-selective cationic channels that can be found as homomers (5-HT3A) or heteromers. The free-leaving nematode Caenorhabditis elegans is a model for the study of the nervous system and for antiparasitic drug discovery. As parasitic nematodes, C. elegans contains a homomeric serotonin-gated chloride channel, MOD-1, that modulates locomotory behavior. The absence of this receptor in vertebrates, converts MOD-1 into a potential antiparasitic drug target. We expressed MOD-1 in mammalian cells and explored by patch-clamp recordings its activation and modulation properties. Dose-response curves revealed an EC50 for 5-HT activation of about 1 µM, which is in the same range as that of human 5-HT3A receptors. The analysis of whole-cell currents determined that MOD-1 channels do not show rectification, desensitize slowly in the presence of 5-HT, and recover from desensitization with a time constant of about 1 s. In contrast to their actions at mammalian 5-HT3 receptors, 5- hydroxyindol and thymol do not potentiate MOD-1 currents. The antiparasitic drug ivermectin (IVM), which acts as activator or potentiator of different Cys-loop receptors, neither activates nor potentiates MOD-1 but pre-exposure to IVM inhibits MOD-1 currents. To gain further insights into the molecular function of the native MOD-1, we sought to identify serotonin-activated chloride channels from C. elegans neurons expressing MOD-1 and compared to MOD-1 channels heterologously expressed in mammalian cells. The understanding of the molecular pharmacology of MOD-1 contributes to our knowledge of the Cys-loop receptor family and to its potential as a novel drug target for anthelmintic therapy.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
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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/11336/163975
Activation and modulation of the caenorhabditis elegans serotonin-gated chloride channel; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Buenos Aires; Argentina; 2019; 207-207
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/163975
identifier_str_mv Activation and modulation of the caenorhabditis elegans serotonin-gated chloride channel; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Buenos Aires; Argentina; 2019; 207-207
0025-7680
1669-9106
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://www.saic.org.ar/revista-medicina
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dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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reponame_str CONICET Digital (CONICET)
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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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