Molecular pharmacology of serotonin-gated chloride channel

Autores
Rodriguez Araujo, Noelia; Bouzat, Cecilia Beatriz; Corradi, Jeremias
Año de publicación
2018
Idioma
español castellano
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 receptors are non-selective cation channels that can be found as homomers (5-HT3A) or heteromers when combined with 5HT3B-E subunits. The free-leaving nematode Caenorhabditis elegans is a model for the study of the nervous system and human diseases, and for antiparasitic drug discovery. C. elegans contains a homomeric serotonin-gated Cys-loop receptor, MOD-1, that is permeable to chloride. We here expressed MOD-1 in mammalian cells and explored the properties of activation and modulation of MOD-1 by whole cell recordings. Dose-response curves showed an EC50 for 5-HT of ~1 mM, which is in the same range as that of human 5-HT3A receptors. The analysis showed that currents do not show rectification, desensitize slowly and recover from desensitization with a time constant of about 1 s. To characterize the pharmacology of MOD-1, we tested compounds that have been shown to modulate 5-HT3 and other Cys-loop receptors. The antiparasitic drug ivermectin (IVM), which acts as an activator or modulator of different receptors, neither activated nor potentiated MOD-1. However, pre-exposure to IVM (10-50 mM) decreased 5-HT induced currents, indicating that it acts as an inhibitor of MOD-1. The 5-HT3 receptor potentiator, 5-hydroxyindol, did not affect MOD-1 function, whereas thymol, which is an activator and/or modulator of 5-HT3 receptors, could only modulate MOD-1 activity. These results contribute to the understanding of the molecular pharmacology of MOD-1 as a potential 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: 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
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
XLVII Reunión Anual de la Sociedad Argentina de Biofísica
La Plata
Argentina
Sociedad Argentina de Investigación en Biofísica
Materia
C.ELEGANS
CYS-LOOP
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:11336/231793
Acceder
id CONICETDig_043dbd2b3a5c1a996f67b31c3240665a
oai_identifier_str oai:ri.conicet.gov.ar:11336/231793
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Molecular pharmacology of serotonin-gated chloride channelRodriguez Araujo, NoeliaBouzat, Cecilia BeatrizCorradi, JeremiasC.ELEGANSCYS-LOOPSEROTONINhttps://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 receptors are non-selective cation channels that can be found as homomers (5-HT3A) or heteromers when combined with 5HT3B-E subunits. The free-leaving nematode Caenorhabditis elegans is a model for the study of the nervous system and human diseases, and for antiparasitic drug discovery. C. elegans contains a homomeric serotonin-gated Cys-loop receptor, MOD-1, that is permeable to chloride. We here expressed MOD-1 in mammalian cells and explored the properties of activation and modulation of MOD-1 by whole cell recordings. Dose-response curves showed an EC50 for 5-HT of ~1 mM, which is in the same range as that of human 5-HT3A receptors. The analysis showed that currents do not show rectification, desensitize slowly and recover from desensitization with a time constant of about 1 s. To characterize the pharmacology of MOD-1, we tested compounds that have been shown to modulate 5-HT3 and other Cys-loop receptors. The antiparasitic drug ivermectin (IVM), which acts as an activator or modulator of different receptors, neither activated nor potentiated MOD-1. However, pre-exposure to IVM (10-50 mM) decreased 5-HT induced currents, indicating that it acts as an inhibitor of MOD-1. The 5-HT3 receptor potentiator, 5-hydroxyindol, did not affect MOD-1 function, whereas thymol, which is an activator and/or modulator of 5-HT3 receptors, could only modulate MOD-1 activity. These results contribute to the understanding of the molecular pharmacology of MOD-1 as a potential drug target for anthelmintic therapyFil: 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; 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; ArgentinaXLVII Reunión Anual de la Sociedad Argentina de BiofísicaLa PlataArgentinaSociedad Argentina de Investigación en BiofísicaSociedad argentina de investigación en biofísicaCelej, Maria SoledadAcierno, Juan Pablo2018info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/231793Molecular pharmacology of serotonin-gated chloride channel; XLVII Reunión Anual de la Sociedad Argentina de Biofísica; La Plata; Argentina; 2018; 113-113978-987-27591-6-2CONICET DigitalCONICETspainfo:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/reuniones-cientificas/reunionsab-previas/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 Técnicas2025-09-03T10:06:28Zoai:ri.conicet.gov.ar:11336/231793instacron: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 10:06:28.33CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Molecular pharmacology of serotonin-gated chloride channel
title Molecular pharmacology of serotonin-gated chloride channel
spellingShingle Molecular pharmacology of serotonin-gated chloride channel
Rodriguez Araujo, Noelia
C.ELEGANS
CYS-LOOP
SEROTONIN
title_short Molecular pharmacology of serotonin-gated chloride channel
title_full Molecular pharmacology of serotonin-gated chloride channel
title_fullStr Molecular pharmacology of serotonin-gated chloride channel
title_full_unstemmed Molecular pharmacology of serotonin-gated chloride channel
title_sort Molecular pharmacology of serotonin-gated chloride channel
dc.creator.none.fl_str_mv Rodriguez Araujo, Noelia
Bouzat, Cecilia Beatriz
Corradi, Jeremias
author Rodriguez Araujo, Noelia
author_facet Rodriguez Araujo, Noelia
Bouzat, Cecilia Beatriz
Corradi, Jeremias
author_role author
author2 Bouzat, Cecilia Beatriz
Corradi, Jeremias
author2_role author
author
dc.contributor.none.fl_str_mv Celej, Maria Soledad
Acierno, Juan Pablo
dc.subject.none.fl_str_mv C.ELEGANS
CYS-LOOP
SEROTONIN
topic C.ELEGANS
CYS-LOOP
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 receptors are non-selective cation channels that can be found as homomers (5-HT3A) or heteromers when combined with 5HT3B-E subunits. The free-leaving nematode Caenorhabditis elegans is a model for the study of the nervous system and human diseases, and for antiparasitic drug discovery. C. elegans contains a homomeric serotonin-gated Cys-loop receptor, MOD-1, that is permeable to chloride. We here expressed MOD-1 in mammalian cells and explored the properties of activation and modulation of MOD-1 by whole cell recordings. Dose-response curves showed an EC50 for 5-HT of ~1 mM, which is in the same range as that of human 5-HT3A receptors. The analysis showed that currents do not show rectification, desensitize slowly and recover from desensitization with a time constant of about 1 s. To characterize the pharmacology of MOD-1, we tested compounds that have been shown to modulate 5-HT3 and other Cys-loop receptors. The antiparasitic drug ivermectin (IVM), which acts as an activator or modulator of different receptors, neither activated nor potentiated MOD-1. However, pre-exposure to IVM (10-50 mM) decreased 5-HT induced currents, indicating that it acts as an inhibitor of MOD-1. The 5-HT3 receptor potentiator, 5-hydroxyindol, did not affect MOD-1 function, whereas thymol, which is an activator and/or modulator of 5-HT3 receptors, could only modulate MOD-1 activity. These results contribute to the understanding of the molecular pharmacology of MOD-1 as a potential 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: 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
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
XLVII Reunión Anual de la Sociedad Argentina de Biofísica
La Plata
Argentina
Sociedad Argentina de Investigación en Biofísica
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 receptors are non-selective cation channels that can be found as homomers (5-HT3A) or heteromers when combined with 5HT3B-E subunits. The free-leaving nematode Caenorhabditis elegans is a model for the study of the nervous system and human diseases, and for antiparasitic drug discovery. C. elegans contains a homomeric serotonin-gated Cys-loop receptor, MOD-1, that is permeable to chloride. We here expressed MOD-1 in mammalian cells and explored the properties of activation and modulation of MOD-1 by whole cell recordings. Dose-response curves showed an EC50 for 5-HT of ~1 mM, which is in the same range as that of human 5-HT3A receptors. The analysis showed that currents do not show rectification, desensitize slowly and recover from desensitization with a time constant of about 1 s. To characterize the pharmacology of MOD-1, we tested compounds that have been shown to modulate 5-HT3 and other Cys-loop receptors. The antiparasitic drug ivermectin (IVM), which acts as an activator or modulator of different receptors, neither activated nor potentiated MOD-1. However, pre-exposure to IVM (10-50 mM) decreased 5-HT induced currents, indicating that it acts as an inhibitor of MOD-1. The 5-HT3 receptor potentiator, 5-hydroxyindol, did not affect MOD-1 function, whereas thymol, which is an activator and/or modulator of 5-HT3 receptors, could only modulate MOD-1 activity. These results contribute to the understanding of the molecular pharmacology of MOD-1 as a potential drug target for anthelmintic therapy
publishDate 2018
dc.date.none.fl_str_mv 2018
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/11336/231793
Molecular pharmacology of serotonin-gated chloride channel; XLVII Reunión Anual de la Sociedad Argentina de Biofísica; La Plata; Argentina; 2018; 113-113
978-987-27591-6-2
CONICET Digital
CONICET
url http://hdl.handle.net/11336/231793
identifier_str_mv Molecular pharmacology of serotonin-gated chloride channel; XLVII Reunión Anual de la Sociedad Argentina de Biofísica; La Plata; Argentina; 2018; 113-113
978-987-27591-6-2
CONICET Digital
CONICET
dc.language.none.fl_str_mv spa
language spa
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/reuniones-cientificas/reunionsab-previas/
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
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad argentina de investigación en biofísica
publisher.none.fl_str_mv Sociedad argentina de investigación en biofísica
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
_version_ 1842269960135507968
score 13.13397

Publicaciones similares