Exploring serotonin-gated ion channels through repurposing strategies

Autores
Rodriguez Araujo, Noelia; Hernando, Guillermina Silvana; Bouzat, Cecilia Beatriz
Año de publicación
2023
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
A drug repurposing strategy that considers the chemical structure and molecular action on serotonergic Cys-loop receptors offers valu- able guidance for the rational reuse of existing drugs, thereby reduc- ing the time and costs associated with developing new medications. We focused on nematode and vertebrate 5-HT-gated ion channels and tested several drugs in clinical use using electrophysiological techniques. In nematodes, a unique serotonin-activated chloride channel, MOD-1, is emerging as a new target for antiparasitic drugs. In humans, 5-HT3A is involved in emesis and is an important player in the enteric nervous system. We previously demonstrated that tryptamine and its derivatives could be good candidates for anthelmintic therapy, acting on the serotonin MOD-1 receptor. We found that sumatriptan and eletriptan, from the triptan family, inhibit 5-HT-induced currents of MOD-1 receptor in a concentration-de- pendent manner. By using the nematode Caenorhabditis elegans, we revealed the anthelmintic actions of sumatriptan and eletriptan at the behavioral level. Our locomotor activity assays showed that both drugs produced a decrease in worms’ activity, with eletriptan being more potent than sumatriptan. Mutants lacking MOD-1 were partially resistant to both drugs. Also, we revealed novel aspects of MOD-1 function from the molecular level to the organism level, which may contribute to provide new directions for anthelmintic drug discovery and drug repurposing. By electrophysiology techniques we revealed that the anthelmintic piperazine (PZE), which acts at nematode GABA and MOD-1 receptors, decreased human 5-HT3A macroscopic currents elicited by 5-HT. The analysis showed that PZE acts as a negative allosteric modulator; thus PZE or its deriv- atives may be explored as promising therapeutic tools that may re- place classical orthosteric antagonists. Our drug repurposing strat- egy contributes to identify new targets and potential uses of drugs on a rational basis
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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Biología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Materia
DRUG REPURPOSING
SEROTONERGIC CYS-LOOP RECEPTORS
CAENORHABDITIS ELEGANS
ION CHANNELS
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:11336/225129
Acceder
id CONICETDig_6c4974bd0ff3af955be62e82e30a34f5
oai_identifier_str oai:ri.conicet.gov.ar:11336/225129
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Exploring serotonin-gated ion channels through repurposing strategiesRodriguez Araujo, NoeliaHernando, Guillermina SilvanaBouzat, Cecilia BeatrizDRUG REPURPOSINGSEROTONERGIC CYS-LOOP RECEPTORSCAENORHABDITIS ELEGANSION CHANNELShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1A drug repurposing strategy that considers the chemical structure and molecular action on serotonergic Cys-loop receptors offers valu- able guidance for the rational reuse of existing drugs, thereby reduc- ing the time and costs associated with developing new medications. We focused on nematode and vertebrate 5-HT-gated ion channels and tested several drugs in clinical use using electrophysiological techniques. In nematodes, a unique serotonin-activated chloride channel, MOD-1, is emerging as a new target for antiparasitic drugs. In humans, 5-HT3A is involved in emesis and is an important player in the enteric nervous system. We previously demonstrated that tryptamine and its derivatives could be good candidates for anthelmintic therapy, acting on the serotonin MOD-1 receptor. We found that sumatriptan and eletriptan, from the triptan family, inhibit 5-HT-induced currents of MOD-1 receptor in a concentration-de- pendent manner. By using the nematode Caenorhabditis elegans, we revealed the anthelmintic actions of sumatriptan and eletriptan at the behavioral level. Our locomotor activity assays showed that both drugs produced a decrease in worms’ activity, with eletriptan being more potent than sumatriptan. Mutants lacking MOD-1 were partially resistant to both drugs. Also, we revealed novel aspects of MOD-1 function from the molecular level to the organism level, which may contribute to provide new directions for anthelmintic drug discovery and drug repurposing. By electrophysiology techniques we revealed that the anthelmintic piperazine (PZE), which acts at nematode GABA and MOD-1 receptors, decreased human 5-HT3A macroscopic currents elicited by 5-HT. The analysis showed that PZE acts as a negative allosteric modulator; thus PZE or its deriv- atives may be explored as promising therapeutic tools that may re- place classical orthosteric antagonists. Our drug repurposing strat- egy contributes to identify new targets and potential uses of drugs on a rational basisFil: 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; 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; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaLXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioMar del PlataArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de BiologíaAsociación Argentina de Farmacología ExperimentalAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioFundación Revista Medicina2023info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/225129Exploring serotonin-gated ion channels through repurposing strategies; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2023; 206-2060025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicinainfo:eu-repo/semantics/altIdentifier/url/https://www.reunionbiociencias.com.ar/wp-content/uploads/2023/11/Revista-Medicina-2023.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 Técnicas2025-09-03T09:57:05Zoai:ri.conicet.gov.ar:11336/225129instacron: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 09:57:05.709CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Exploring serotonin-gated ion channels through repurposing strategies
title Exploring serotonin-gated ion channels through repurposing strategies
spellingShingle Exploring serotonin-gated ion channels through repurposing strategies
Rodriguez Araujo, Noelia
DRUG REPURPOSING
SEROTONERGIC CYS-LOOP RECEPTORS
CAENORHABDITIS ELEGANS
ION CHANNELS
title_short Exploring serotonin-gated ion channels through repurposing strategies
title_full Exploring serotonin-gated ion channels through repurposing strategies
title_fullStr Exploring serotonin-gated ion channels through repurposing strategies
title_full_unstemmed Exploring serotonin-gated ion channels through repurposing strategies
title_sort Exploring serotonin-gated ion channels through repurposing strategies
dc.creator.none.fl_str_mv Rodriguez Araujo, Noelia
Hernando, Guillermina Silvana
Bouzat, Cecilia Beatriz
author Rodriguez Araujo, Noelia
author_facet Rodriguez Araujo, Noelia
Hernando, Guillermina Silvana
Bouzat, Cecilia Beatriz
author_role author
author2 Hernando, Guillermina Silvana
Bouzat, Cecilia Beatriz
author2_role author
author
dc.subject.none.fl_str_mv DRUG REPURPOSING
SEROTONERGIC CYS-LOOP RECEPTORS
CAENORHABDITIS ELEGANS
ION CHANNELS
topic DRUG REPURPOSING
SEROTONERGIC CYS-LOOP RECEPTORS
CAENORHABDITIS ELEGANS
ION CHANNELS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv A drug repurposing strategy that considers the chemical structure and molecular action on serotonergic Cys-loop receptors offers valu- able guidance for the rational reuse of existing drugs, thereby reduc- ing the time and costs associated with developing new medications. We focused on nematode and vertebrate 5-HT-gated ion channels and tested several drugs in clinical use using electrophysiological techniques. In nematodes, a unique serotonin-activated chloride channel, MOD-1, is emerging as a new target for antiparasitic drugs. In humans, 5-HT3A is involved in emesis and is an important player in the enteric nervous system. We previously demonstrated that tryptamine and its derivatives could be good candidates for anthelmintic therapy, acting on the serotonin MOD-1 receptor. We found that sumatriptan and eletriptan, from the triptan family, inhibit 5-HT-induced currents of MOD-1 receptor in a concentration-de- pendent manner. By using the nematode Caenorhabditis elegans, we revealed the anthelmintic actions of sumatriptan and eletriptan at the behavioral level. Our locomotor activity assays showed that both drugs produced a decrease in worms’ activity, with eletriptan being more potent than sumatriptan. Mutants lacking MOD-1 were partially resistant to both drugs. Also, we revealed novel aspects of MOD-1 function from the molecular level to the organism level, which may contribute to provide new directions for anthelmintic drug discovery and drug repurposing. By electrophysiology techniques we revealed that the anthelmintic piperazine (PZE), which acts at nematode GABA and MOD-1 receptors, decreased human 5-HT3A macroscopic currents elicited by 5-HT. The analysis showed that PZE acts as a negative allosteric modulator; thus PZE or its deriv- atives may be explored as promising therapeutic tools that may re- place classical orthosteric antagonists. Our drug repurposing strat- egy contributes to identify new targets and potential uses of drugs on a rational basis
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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Biología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
description A drug repurposing strategy that considers the chemical structure and molecular action on serotonergic Cys-loop receptors offers valu- able guidance for the rational reuse of existing drugs, thereby reduc- ing the time and costs associated with developing new medications. We focused on nematode and vertebrate 5-HT-gated ion channels and tested several drugs in clinical use using electrophysiological techniques. In nematodes, a unique serotonin-activated chloride channel, MOD-1, is emerging as a new target for antiparasitic drugs. In humans, 5-HT3A is involved in emesis and is an important player in the enteric nervous system. We previously demonstrated that tryptamine and its derivatives could be good candidates for anthelmintic therapy, acting on the serotonin MOD-1 receptor. We found that sumatriptan and eletriptan, from the triptan family, inhibit 5-HT-induced currents of MOD-1 receptor in a concentration-de- pendent manner. By using the nematode Caenorhabditis elegans, we revealed the anthelmintic actions of sumatriptan and eletriptan at the behavioral level. Our locomotor activity assays showed that both drugs produced a decrease in worms’ activity, with eletriptan being more potent than sumatriptan. Mutants lacking MOD-1 were partially resistant to both drugs. Also, we revealed novel aspects of MOD-1 function from the molecular level to the organism level, which may contribute to provide new directions for anthelmintic drug discovery and drug repurposing. By electrophysiology techniques we revealed that the anthelmintic piperazine (PZE), which acts at nematode GABA and MOD-1 receptors, decreased human 5-HT3A macroscopic currents elicited by 5-HT. The analysis showed that PZE acts as a negative allosteric modulator; thus PZE or its deriv- atives may be explored as promising therapeutic tools that may re- place classical orthosteric antagonists. Our drug repurposing strat- egy contributes to identify new targets and potential uses of drugs on a rational basis
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
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/11336/225129
Exploring serotonin-gated ion channels through repurposing strategies; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2023; 206-206
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/225129
identifier_str_mv Exploring serotonin-gated ion channels through repurposing strategies; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; XXV Jornadas Anuales de la Sociedad Argentina de Biología; LV Reunión Anual de la Asociación Argentina de Farmacología Experimental y VIII Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio; Mar del Plata; Argentina; 2023; 206-206
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
info:eu-repo/semantics/altIdentifier/url/https://www.reunionbiociencias.com.ar/wp-content/uploads/2023/11/Revista-Medicina-2023.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
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)
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_ 1842269439089704960
score 13.13397

Publicaciones similares