Characterization of a neuronal-like GABAergic system in human lymphocytes

Autores
de Rosa, Maria Jose; Dionisio, Leonardo Raul; Bouzat, Cecilia Beatriz; Esandi, María del Carmen
Año de publicación
2010
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
GABA is a major neurotransmitter in the central nervous system. Here we identified components of the GABAergic system in human lymphocytes and determined their functional role. By RT-PCR we first detected mRNA of different components of this system in resting and mitogen-activated lymphocytes: i) GAD67, an isoform of the enzyme that synthetizes GABA; ii) VIAAT, the vesicular protein involved in GABA store; iii) GABA transporter (GAT1-2); iv) GABA-T, the enzyme that catabolizes GABA; and v) alpha1 and rho2 subunits that conform ionotropic GABA receptors. In addition we performed immunocytochemistry to detect VIAAT protein and real time PCR to quantify mRNA levels of GABA-T. We observed upregulation of VIAAT and GABA-T upon mitogen stimulation. We also measured the functionality of GABA transporters by measuring uptake of radioactive GABA. The results demonstrate that GABA uptake is significantly increased in activated lymphocytes. To determine if GABA subunits assemble into functional channels, we performed whole-cell recordings in activated lymphocytes. GABA and muscimol, a specific agonist for ionotropic GABA receptors, elicit currents in about 10-15% of the cells. These experiments show that lymphocytes express functional GABA-activated channels. Finally, using [3H]thymidine incorporation, we established that GABA is able to modulate negatively lymphocyte proliferation. Muscimol, similarly to GABA, inhibits lymphocyte proliferation, thus suggesting that this action is mediated by ionotropic GABA receptors. Taken together, our results reveal that lymphocytes have most of the essential components needed to constitute a neuronal-like GABAergic system. Pharmacological modulation of this system may provide new approaches for regulation of T cell response
Fil: de Rosa, Maria Jose. 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: Dionisio, Leonardo Raul. 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: Esandi, María del Carmen. 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; Argentina
40th Annual Meeting Society for Neuroscience
San Diego
Estados Unidos
Society for Neuroscience
Materia
LYMPHOCYTES
GABAERGIC SYSTEM
ACTIVATION
MACROSCOPIC CURRENTS
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:11336/231913
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/231913
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Characterization of a neuronal-like GABAergic system in human lymphocytesde Rosa, Maria JoseDionisio, Leonardo RaulBouzat, Cecilia BeatrizEsandi, María del CarmenLYMPHOCYTESGABAERGIC SYSTEMACTIVATIONMACROSCOPIC CURRENTShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3GABA is a major neurotransmitter in the central nervous system. Here we identified components of the GABAergic system in human lymphocytes and determined their functional role. By RT-PCR we first detected mRNA of different components of this system in resting and mitogen-activated lymphocytes: i) GAD67, an isoform of the enzyme that synthetizes GABA; ii) VIAAT, the vesicular protein involved in GABA store; iii) GABA transporter (GAT1-2); iv) GABA-T, the enzyme that catabolizes GABA; and v) alpha1 and rho2 subunits that conform ionotropic GABA receptors. In addition we performed immunocytochemistry to detect VIAAT protein and real time PCR to quantify mRNA levels of GABA-T. We observed upregulation of VIAAT and GABA-T upon mitogen stimulation. We also measured the functionality of GABA transporters by measuring uptake of radioactive GABA. The results demonstrate that GABA uptake is significantly increased in activated lymphocytes. To determine if GABA subunits assemble into functional channels, we performed whole-cell recordings in activated lymphocytes. GABA and muscimol, a specific agonist for ionotropic GABA receptors, elicit currents in about 10-15% of the cells. These experiments show that lymphocytes express functional GABA-activated channels. Finally, using [3H]thymidine incorporation, we established that GABA is able to modulate negatively lymphocyte proliferation. Muscimol, similarly to GABA, inhibits lymphocyte proliferation, thus suggesting that this action is mediated by ionotropic GABA receptors. Taken together, our results reveal that lymphocytes have most of the essential components needed to constitute a neuronal-like GABAergic system. Pharmacological modulation of this system may provide new approaches for regulation of T cell responseFil: de Rosa, Maria Jose. 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: Dionisio, Leonardo Raul. 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: Esandi, María del Carmen. 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; Argentina40th Annual Meeting Society for NeuroscienceSan DiegoEstados UnidosSociety for NeuroscienceSociety for Neuroscience2010info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/231913Characterization of a neuronal-like GABAergic system in human lymphocytes; 40th Annual Meeting Society for Neuroscience; San Diego; Estados Unidos; 2010; 1-1CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sfn.org/meetings/past-and-future-annual-meetingsinfo:eu-repo/semantics/altIdentifier/url/https://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=2554&sKey=4f5ffce6-dd3c-4d8d-8107-4e29b4b06b79&cKey=b7e887e0-10f5-41b6-b56e-a3f1c3c49412&mKey=e5d5c83f-ce2d-4d71-9dd6-fc7231e090fbInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:49:09Zoai:ri.conicet.gov.ar:11336/231913instacron: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 09:49:09.531CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Characterization of a neuronal-like GABAergic system in human lymphocytes
title Characterization of a neuronal-like GABAergic system in human lymphocytes
spellingShingle Characterization of a neuronal-like GABAergic system in human lymphocytes
de Rosa, Maria Jose
LYMPHOCYTES
GABAERGIC SYSTEM
ACTIVATION
MACROSCOPIC CURRENTS
title_short Characterization of a neuronal-like GABAergic system in human lymphocytes
title_full Characterization of a neuronal-like GABAergic system in human lymphocytes
title_fullStr Characterization of a neuronal-like GABAergic system in human lymphocytes
title_full_unstemmed Characterization of a neuronal-like GABAergic system in human lymphocytes
title_sort Characterization of a neuronal-like GABAergic system in human lymphocytes
dc.creator.none.fl_str_mv de Rosa, Maria Jose
Dionisio, Leonardo Raul
Bouzat, Cecilia Beatriz
Esandi, María del Carmen
author de Rosa, Maria Jose
author_facet de Rosa, Maria Jose
Dionisio, Leonardo Raul
Bouzat, Cecilia Beatriz
Esandi, María del Carmen
author_role author
author2 Dionisio, Leonardo Raul
Bouzat, Cecilia Beatriz
Esandi, María del Carmen
author2_role author
author
author
dc.subject.none.fl_str_mv LYMPHOCYTES
GABAERGIC SYSTEM
ACTIVATION
MACROSCOPIC CURRENTS
topic LYMPHOCYTES
GABAERGIC SYSTEM
ACTIVATION
MACROSCOPIC CURRENTS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv GABA is a major neurotransmitter in the central nervous system. Here we identified components of the GABAergic system in human lymphocytes and determined their functional role. By RT-PCR we first detected mRNA of different components of this system in resting and mitogen-activated lymphocytes: i) GAD67, an isoform of the enzyme that synthetizes GABA; ii) VIAAT, the vesicular protein involved in GABA store; iii) GABA transporter (GAT1-2); iv) GABA-T, the enzyme that catabolizes GABA; and v) alpha1 and rho2 subunits that conform ionotropic GABA receptors. In addition we performed immunocytochemistry to detect VIAAT protein and real time PCR to quantify mRNA levels of GABA-T. We observed upregulation of VIAAT and GABA-T upon mitogen stimulation. We also measured the functionality of GABA transporters by measuring uptake of radioactive GABA. The results demonstrate that GABA uptake is significantly increased in activated lymphocytes. To determine if GABA subunits assemble into functional channels, we performed whole-cell recordings in activated lymphocytes. GABA and muscimol, a specific agonist for ionotropic GABA receptors, elicit currents in about 10-15% of the cells. These experiments show that lymphocytes express functional GABA-activated channels. Finally, using [3H]thymidine incorporation, we established that GABA is able to modulate negatively lymphocyte proliferation. Muscimol, similarly to GABA, inhibits lymphocyte proliferation, thus suggesting that this action is mediated by ionotropic GABA receptors. Taken together, our results reveal that lymphocytes have most of the essential components needed to constitute a neuronal-like GABAergic system. Pharmacological modulation of this system may provide new approaches for regulation of T cell response
Fil: de Rosa, Maria Jose. 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: Dionisio, Leonardo Raul. 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: Esandi, María del Carmen. 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; Argentina
40th Annual Meeting Society for Neuroscience
San Diego
Estados Unidos
Society for Neuroscience
description GABA is a major neurotransmitter in the central nervous system. Here we identified components of the GABAergic system in human lymphocytes and determined their functional role. By RT-PCR we first detected mRNA of different components of this system in resting and mitogen-activated lymphocytes: i) GAD67, an isoform of the enzyme that synthetizes GABA; ii) VIAAT, the vesicular protein involved in GABA store; iii) GABA transporter (GAT1-2); iv) GABA-T, the enzyme that catabolizes GABA; and v) alpha1 and rho2 subunits that conform ionotropic GABA receptors. In addition we performed immunocytochemistry to detect VIAAT protein and real time PCR to quantify mRNA levels of GABA-T. We observed upregulation of VIAAT and GABA-T upon mitogen stimulation. We also measured the functionality of GABA transporters by measuring uptake of radioactive GABA. The results demonstrate that GABA uptake is significantly increased in activated lymphocytes. To determine if GABA subunits assemble into functional channels, we performed whole-cell recordings in activated lymphocytes. GABA and muscimol, a specific agonist for ionotropic GABA receptors, elicit currents in about 10-15% of the cells. These experiments show that lymphocytes express functional GABA-activated channels. Finally, using [3H]thymidine incorporation, we established that GABA is able to modulate negatively lymphocyte proliferation. Muscimol, similarly to GABA, inhibits lymphocyte proliferation, thus suggesting that this action is mediated by ionotropic GABA receptors. Taken together, our results reveal that lymphocytes have most of the essential components needed to constitute a neuronal-like GABAergic system. Pharmacological modulation of this system may provide new approaches for regulation of T cell response
publishDate 2010
dc.date.none.fl_str_mv 2010
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/11336/231913
Characterization of a neuronal-like GABAergic system in human lymphocytes; 40th Annual Meeting Society for Neuroscience; San Diego; Estados Unidos; 2010; 1-1
CONICET Digital
CONICET
url http://hdl.handle.net/11336/231913
identifier_str_mv Characterization of a neuronal-like GABAergic system in human lymphocytes; 40th Annual Meeting Society for Neuroscience; San Diego; Estados Unidos; 2010; 1-1
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.sfn.org/meetings/past-and-future-annual-meetings
info:eu-repo/semantics/altIdentifier/url/https://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=2554&sKey=4f5ffce6-dd3c-4d8d-8107-4e29b4b06b79&cKey=b7e887e0-10f5-41b6-b56e-a3f1c3c49412&mKey=e5d5c83f-ce2d-4d71-9dd6-fc7231e090fb
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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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 Internacional
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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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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