Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors

Autores
Rothlin, Carla; Lioudyno, Maria I.; Silbering, Ana F.; Plazas, Paola Viviana; Gomez Casati, Maria Eugenia; Katz, Eleonora; Guth, Paul S.; Elgoyhen, Ana Belen
Año de publicación
2003
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In the present work, we characterized the effects of serotonin type 3 receptor ligands on recombinant and native α9α10-containing nicotinic acetylcholine receptors (nAChRs). Our results indicate that the recombinant α9α10 nAChR shares striking pharmacological properties with 5-HT3 ligand-gated ion channels. Thus, 5-HT3 receptor antagonists block ACh-evoked currents in α9α10-injected Xenopus laevis oocytes with a rank order of potency of tropisetron (IC50, 70.1 ± 0.9 nM) > ondansetron (IC50, 0.6 ± 0.1 μM) = MDL 72222 (IC50, 0.7 ± 0.1 μM). Although serotonin does not elicit responses in α9α10-injected oocytes, it blocks recombinant α9α10 receptors in a noncompetitive and voltage-dependent manner (IC50, 5.4 ± 0.6 μM). On the other hand, we demonstrate an in vivo correlate of these properties of the recombinant receptor, with those of the α9α10-containing nAChR of frog saccular hair cells. The possibility that the biogenic amine serotonin might act as a neuromodulator of the cholinergic efferent transmission in the vestibular apparatus and in the organ of Corti is discussed.
Fil: Rothlin, Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Lioudyno, Maria I.. Tulane University; Estados Unidos
Fil: Silbering, Ana F.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Plazas, Paola Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Gomez Casati, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Katz, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad Nacional de Córdoba. Facultad de Cs.exactas Físicas y Naturales. Departamento de Biología; Argentina
Fil: Guth, Paul S.. Tulane University; Estados Unidos
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Materia
Nicotinic Cholinergic Receptors
Acetylcholine
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:11336/79766
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/79766
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptorsRothlin, CarlaLioudyno, Maria I.Silbering, Ana F.Plazas, Paola VivianaGomez Casati, Maria EugeniaKatz, EleonoraGuth, Paul S.Elgoyhen, Ana BelenNicotinic Cholinergic ReceptorsAcetylcholinehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1In the present work, we characterized the effects of serotonin type 3 receptor ligands on recombinant and native α9α10-containing nicotinic acetylcholine receptors (nAChRs). Our results indicate that the recombinant α9α10 nAChR shares striking pharmacological properties with 5-HT3 ligand-gated ion channels. Thus, 5-HT3 receptor antagonists block ACh-evoked currents in α9α10-injected Xenopus laevis oocytes with a rank order of potency of tropisetron (IC50, 70.1 ± 0.9 nM) > ondansetron (IC50, 0.6 ± 0.1 μM) = MDL 72222 (IC50, 0.7 ± 0.1 μM). Although serotonin does not elicit responses in α9α10-injected oocytes, it blocks recombinant α9α10 receptors in a noncompetitive and voltage-dependent manner (IC50, 5.4 ± 0.6 μM). On the other hand, we demonstrate an in vivo correlate of these properties of the recombinant receptor, with those of the α9α10-containing nAChR of frog saccular hair cells. The possibility that the biogenic amine serotonin might act as a neuromodulator of the cholinergic efferent transmission in the vestibular apparatus and in the organ of Corti is discussed.Fil: Rothlin, Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lioudyno, Maria I.. Tulane University; Estados UnidosFil: Silbering, Ana F.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Plazas, Paola Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Gomez Casati, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Katz, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad Nacional de Córdoba. Facultad de Cs.exactas Físicas y Naturales. Departamento de Biología; ArgentinaFil: Guth, Paul S.. Tulane University; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaAmerican Society for Pharmacology and Experimental Therapeutics2003-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/79766Rothlin, Carla; Lioudyno, Maria I.; Silbering, Ana F.; Plazas, Paola Viviana; Gomez Casati, Maria Eugenia; et al.; Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors; American Society for Pharmacology and Experimental Therapeutics; Molecular Pharmacology; 63; 5; 5-2003; 1067-10740026-895XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/12695535info:eu-repo/semantics/altIdentifier/doi/10.1124/mol.63.5.1067info:eu-repo/semantics/altIdentifier/url/http://molpharm.aspetjournals.org/content/63/5/1067info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:41:05Zoai:ri.conicet.gov.ar:11336/79766instacron: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 10:41:05.27CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors
title Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors
spellingShingle Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors
Rothlin, Carla
Nicotinic Cholinergic Receptors
Acetylcholine
title_short Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors
title_full Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors
title_fullStr Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors
title_full_unstemmed Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors
title_sort Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors
dc.creator.none.fl_str_mv Rothlin, Carla
Lioudyno, Maria I.
Silbering, Ana F.
Plazas, Paola Viviana
Gomez Casati, Maria Eugenia
Katz, Eleonora
Guth, Paul S.
Elgoyhen, Ana Belen
author Rothlin, Carla
author_facet Rothlin, Carla
Lioudyno, Maria I.
Silbering, Ana F.
Plazas, Paola Viviana
Gomez Casati, Maria Eugenia
Katz, Eleonora
Guth, Paul S.
Elgoyhen, Ana Belen
author_role author
author2 Lioudyno, Maria I.
Silbering, Ana F.
Plazas, Paola Viviana
Gomez Casati, Maria Eugenia
Katz, Eleonora
Guth, Paul S.
Elgoyhen, Ana Belen
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Nicotinic Cholinergic Receptors
Acetylcholine
topic Nicotinic Cholinergic Receptors
Acetylcholine
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In the present work, we characterized the effects of serotonin type 3 receptor ligands on recombinant and native α9α10-containing nicotinic acetylcholine receptors (nAChRs). Our results indicate that the recombinant α9α10 nAChR shares striking pharmacological properties with 5-HT3 ligand-gated ion channels. Thus, 5-HT3 receptor antagonists block ACh-evoked currents in α9α10-injected Xenopus laevis oocytes with a rank order of potency of tropisetron (IC50, 70.1 ± 0.9 nM) > ondansetron (IC50, 0.6 ± 0.1 μM) = MDL 72222 (IC50, 0.7 ± 0.1 μM). Although serotonin does not elicit responses in α9α10-injected oocytes, it blocks recombinant α9α10 receptors in a noncompetitive and voltage-dependent manner (IC50, 5.4 ± 0.6 μM). On the other hand, we demonstrate an in vivo correlate of these properties of the recombinant receptor, with those of the α9α10-containing nAChR of frog saccular hair cells. The possibility that the biogenic amine serotonin might act as a neuromodulator of the cholinergic efferent transmission in the vestibular apparatus and in the organ of Corti is discussed.
Fil: Rothlin, Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Lioudyno, Maria I.. Tulane University; Estados Unidos
Fil: Silbering, Ana F.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Plazas, Paola Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Gomez Casati, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Katz, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad Nacional de Córdoba. Facultad de Cs.exactas Físicas y Naturales. Departamento de Biología; Argentina
Fil: Guth, Paul S.. Tulane University; Estados Unidos
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
description In the present work, we characterized the effects of serotonin type 3 receptor ligands on recombinant and native α9α10-containing nicotinic acetylcholine receptors (nAChRs). Our results indicate that the recombinant α9α10 nAChR shares striking pharmacological properties with 5-HT3 ligand-gated ion channels. Thus, 5-HT3 receptor antagonists block ACh-evoked currents in α9α10-injected Xenopus laevis oocytes with a rank order of potency of tropisetron (IC50, 70.1 ± 0.9 nM) > ondansetron (IC50, 0.6 ± 0.1 μM) = MDL 72222 (IC50, 0.7 ± 0.1 μM). Although serotonin does not elicit responses in α9α10-injected oocytes, it blocks recombinant α9α10 receptors in a noncompetitive and voltage-dependent manner (IC50, 5.4 ± 0.6 μM). On the other hand, we demonstrate an in vivo correlate of these properties of the recombinant receptor, with those of the α9α10-containing nAChR of frog saccular hair cells. The possibility that the biogenic amine serotonin might act as a neuromodulator of the cholinergic efferent transmission in the vestibular apparatus and in the organ of Corti is discussed.
publishDate 2003
dc.date.none.fl_str_mv 2003-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/79766
Rothlin, Carla; Lioudyno, Maria I.; Silbering, Ana F.; Plazas, Paola Viviana; Gomez Casati, Maria Eugenia; et al.; Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors; American Society for Pharmacology and Experimental Therapeutics; Molecular Pharmacology; 63; 5; 5-2003; 1067-1074
0026-895X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79766
identifier_str_mv Rothlin, Carla; Lioudyno, Maria I.; Silbering, Ana F.; Plazas, Paola Viviana; Gomez Casati, Maria Eugenia; et al.; Direct interaction of serotonin type 3 receptor ligands with recombinant and native α9α10-containing nicotinic cholinergic receptors; American Society for Pharmacology and Experimental Therapeutics; Molecular Pharmacology; 63; 5; 5-2003; 1067-1074
0026-895X
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.ncbi.nlm.nih.gov/pubmed/12695535
info:eu-repo/semantics/altIdentifier/doi/10.1124/mol.63.5.1067
info:eu-repo/semantics/altIdentifier/url/http://molpharm.aspetjournals.org/content/63/5/1067
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.publisher.none.fl_str_mv American Society for Pharmacology and Experimental Therapeutics
publisher.none.fl_str_mv American Society for Pharmacology and Experimental Therapeutics
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 13.070432

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