5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems

Autores
Corradi, Jeremias; Thompson, Andrew; McGonigle, Ian; Price, Kerry L.; Bouzat, Cecilia Beatriz; Lummis, Sarah C.R.
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Genes for five different 5-HT 3 receptor subunits have been identified. Most of the subunits have multiple isoforms, but two isoforms of the B subunits, brain-type 1 (Br1) and brain-type 2 (Br2) are of particular interest as they appear to be abundantly expressed in human brain, where 5-HT3B subunit RNA consists of approximately 75% 5-HT3Br2, 24% 5-HT3Br1, and <1% 5-HT3B. Here we use two-electrode voltage-clamp, radioligand binding, fluorescence, whole cell, and single channel patch-clamp studies to characterize the roles of 5-HT3Br1 and 5-HT3Br2 subunits on function and pharmacology in heterologously expressed 5-HT 3 receptors. The data show that the 5-HT3Br1 transcriptional variant, when coexpressed with 5-HT3A subunits, alters the EC 50 , n H , and single channel conductance of the 5-HT 3 receptor, but has no effect on the potency of competitive antagonists; thus, 5-HT 3 ABr1 receptors have the same characteristics as 5-HT 3 AB receptors. There were some differences in the shapes of 5-HT 3 AB and 5-HT 3 ABr1 receptor responses, which were likely due to a greater proportion of homomeric 5-HT 3 A versus heteromeric 5-HT 3 ABr1 receptors in the latter, as expression of the 5-HT3Br1 compared to the 5-HT3B subunit is less efficient. Conversely, the 5-HT3Br2 subunit does not appear to form functional channels with the 5-HT3A subunit in either oocytes or HEK293 cells, and the role of this subunit is yet to be determined.
Fil: Corradi, Jeremias. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina
Fil: Thompson, Andrew. University Of Cambridge; Reino Unido
Fil: McGonigle, Ian. University Of Cambridge; Reino Unido
Fil: Price, Kerry L.. University Of Cambridge; Reino Unido
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina
Fil: Lummis, Sarah C.R.. University of Cambridge; Reino Unido
Materia
Serotonin
Cys-Loop
Heteromeric
Single-Channel
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/4379
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/4379
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous SystemsCorradi, JeremiasThompson, AndrewMcGonigle, IanPrice, Kerry L.Bouzat, Cecilia BeatrizLummis, Sarah C.R.SerotoninCys-LoopHeteromericSingle-Channelhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Genes for five different 5-HT 3 receptor subunits have been identified. Most of the subunits have multiple isoforms, but two isoforms of the B subunits, brain-type 1 (Br1) and brain-type 2 (Br2) are of particular interest as they appear to be abundantly expressed in human brain, where 5-HT3B subunit RNA consists of approximately 75% 5-HT3Br2, 24% 5-HT3Br1, and <1% 5-HT3B. Here we use two-electrode voltage-clamp, radioligand binding, fluorescence, whole cell, and single channel patch-clamp studies to characterize the roles of 5-HT3Br1 and 5-HT3Br2 subunits on function and pharmacology in heterologously expressed 5-HT 3 receptors. The data show that the 5-HT3Br1 transcriptional variant, when coexpressed with 5-HT3A subunits, alters the EC 50 , n H , and single channel conductance of the 5-HT 3 receptor, but has no effect on the potency of competitive antagonists; thus, 5-HT 3 ABr1 receptors have the same characteristics as 5-HT 3 AB receptors. There were some differences in the shapes of 5-HT 3 AB and 5-HT 3 ABr1 receptor responses, which were likely due to a greater proportion of homomeric 5-HT 3 A versus heteromeric 5-HT 3 ABr1 receptors in the latter, as expression of the 5-HT3Br1 compared to the 5-HT3B subunit is less efficient. Conversely, the 5-HT3Br2 subunit does not appear to form functional channels with the 5-HT3A subunit in either oocytes or HEK293 cells, and the role of this subunit is yet to be determined.Fil: Corradi, Jeremias. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); ArgentinaFil: Thompson, Andrew. University Of Cambridge; Reino UnidoFil: McGonigle, Ian. University Of Cambridge; Reino UnidoFil: Price, Kerry L.. University Of Cambridge; Reino UnidoFil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); ArgentinaFil: Lummis, Sarah C.R.. University of Cambridge; Reino UnidoAmerican Chemical Society2015-05info: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/11336/4379Corradi, Jeremias; Thompson, Andrew; McGonigle, Ian; Price, Kerry L.; Bouzat, Cecilia Beatriz; et al.; 5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems; American Chemical Society; ACS Chemical Neuroscience; 5-2015; 1-71948-7193enginfo:eu-repo/semantics/altIdentifier/ark/10.1021/acschemneuro.5b00080info:eu-repo/semantics/altIdentifier/doi/10.1021/acschemneuro.5b00080info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:49:56Zoai:ri.conicet.gov.ar:11336/4379instacron: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 09:49:56.642CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems
title 5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems
spellingShingle 5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems
Corradi, Jeremias
Serotonin
Cys-Loop
Heteromeric
Single-Channel
title_short 5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems
title_full 5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems
title_fullStr 5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems
title_full_unstemmed 5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems
title_sort 5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems
dc.creator.none.fl_str_mv Corradi, Jeremias
Thompson, Andrew
McGonigle, Ian
Price, Kerry L.
Bouzat, Cecilia Beatriz
Lummis, Sarah C.R.
author Corradi, Jeremias
author_facet Corradi, Jeremias
Thompson, Andrew
McGonigle, Ian
Price, Kerry L.
Bouzat, Cecilia Beatriz
Lummis, Sarah C.R.
author_role author
author2 Thompson, Andrew
McGonigle, Ian
Price, Kerry L.
Bouzat, Cecilia Beatriz
Lummis, Sarah C.R.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Serotonin
Cys-Loop
Heteromeric
Single-Channel
topic Serotonin
Cys-Loop
Heteromeric
Single-Channel
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Genes for five different 5-HT 3 receptor subunits have been identified. Most of the subunits have multiple isoforms, but two isoforms of the B subunits, brain-type 1 (Br1) and brain-type 2 (Br2) are of particular interest as they appear to be abundantly expressed in human brain, where 5-HT3B subunit RNA consists of approximately 75% 5-HT3Br2, 24% 5-HT3Br1, and <1% 5-HT3B. Here we use two-electrode voltage-clamp, radioligand binding, fluorescence, whole cell, and single channel patch-clamp studies to characterize the roles of 5-HT3Br1 and 5-HT3Br2 subunits on function and pharmacology in heterologously expressed 5-HT 3 receptors. The data show that the 5-HT3Br1 transcriptional variant, when coexpressed with 5-HT3A subunits, alters the EC 50 , n H , and single channel conductance of the 5-HT 3 receptor, but has no effect on the potency of competitive antagonists; thus, 5-HT 3 ABr1 receptors have the same characteristics as 5-HT 3 AB receptors. There were some differences in the shapes of 5-HT 3 AB and 5-HT 3 ABr1 receptor responses, which were likely due to a greater proportion of homomeric 5-HT 3 A versus heteromeric 5-HT 3 ABr1 receptors in the latter, as expression of the 5-HT3Br1 compared to the 5-HT3B subunit is less efficient. Conversely, the 5-HT3Br2 subunit does not appear to form functional channels with the 5-HT3A subunit in either oocytes or HEK293 cells, and the role of this subunit is yet to be determined.
Fil: Corradi, Jeremias. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina
Fil: Thompson, Andrew. University Of Cambridge; Reino Unido
Fil: McGonigle, Ian. University Of Cambridge; Reino Unido
Fil: Price, Kerry L.. University Of Cambridge; Reino Unido
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina
Fil: Lummis, Sarah C.R.. University of Cambridge; Reino Unido
description Genes for five different 5-HT 3 receptor subunits have been identified. Most of the subunits have multiple isoforms, but two isoforms of the B subunits, brain-type 1 (Br1) and brain-type 2 (Br2) are of particular interest as they appear to be abundantly expressed in human brain, where 5-HT3B subunit RNA consists of approximately 75% 5-HT3Br2, 24% 5-HT3Br1, and <1% 5-HT3B. Here we use two-electrode voltage-clamp, radioligand binding, fluorescence, whole cell, and single channel patch-clamp studies to characterize the roles of 5-HT3Br1 and 5-HT3Br2 subunits on function and pharmacology in heterologously expressed 5-HT 3 receptors. The data show that the 5-HT3Br1 transcriptional variant, when coexpressed with 5-HT3A subunits, alters the EC 50 , n H , and single channel conductance of the 5-HT 3 receptor, but has no effect on the potency of competitive antagonists; thus, 5-HT 3 ABr1 receptors have the same characteristics as 5-HT 3 AB receptors. There were some differences in the shapes of 5-HT 3 AB and 5-HT 3 ABr1 receptor responses, which were likely due to a greater proportion of homomeric 5-HT 3 A versus heteromeric 5-HT 3 ABr1 receptors in the latter, as expression of the 5-HT3Br1 compared to the 5-HT3B subunit is less efficient. Conversely, the 5-HT3Br2 subunit does not appear to form functional channels with the 5-HT3A subunit in either oocytes or HEK293 cells, and the role of this subunit is yet to be determined.
publishDate 2015
dc.date.none.fl_str_mv 2015-05
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/11336/4379
Corradi, Jeremias; Thompson, Andrew; McGonigle, Ian; Price, Kerry L.; Bouzat, Cecilia Beatriz; et al.; 5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems; American Chemical Society; ACS Chemical Neuroscience; 5-2015; 1-7
1948-7193
url http://hdl.handle.net/11336/4379
identifier_str_mv Corradi, Jeremias; Thompson, Andrew; McGonigle, Ian; Price, Kerry L.; Bouzat, Cecilia Beatriz; et al.; 5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems; American Chemical Society; ACS Chemical Neuroscience; 5-2015; 1-7
1948-7193
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/ark/10.1021/acschemneuro.5b00080
info:eu-repo/semantics/altIdentifier/doi/10.1021/acschemneuro.5b00080
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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_ 1842269003234410496
score 13.13397

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