Quantitative analysis of the dopamine D4 receptor in the mouse brain

Autores
Defagot, Maria Cristina; Falzone, Tomas Luis; Low, Malcolm J.; Grandy, David K.; Rubinstein, Marcelo; Antonelli, Marta Cristina
Año de publicación
2000
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The D4 receptor (D4R), a member of the dopamine D2-like receptor family, has been implicated in the pathophysiology of several diseases and has been the target of various investigations regarding its distribution and quantification. The brain distribution of the D4R has been well described in various species, but the quantification is still an issue of controversy, because no specific ligand is commercially available. To circumvent this difficulty we have performed a biochemical and autoradiographical study in brain samples obtained from mice lacking D4Rs and their wild-type siblings; comparison of their binding parameters allows a more accurate quantification of the members of the D2-like receptor family (D2, D3, and D4 receptors). We found that the distribution of D2-like receptors in mouse brain is similar to that of rat brain, i.e., caudate putamen, nucleus accumbens, olfactory tubercle, and hippocampus. The contribution of the D4R to the overall population of D2-like receptors is 17% in nucleus accumbens, 21% in caudate putamen and olfactory tubercle, and 40% in hippocampus. Based on our study we conclude that nemonapride probably binds to nondopaminergic sites that if not properly blocked may lead to overestimations of D4R levels. We observed that the experimental condition that better estimates the density of D4 receptors is the displacement of D2 and D3 [3H]nemonapride binding sites with cold raclopride.
Fil: Defagot, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Falzone, Tomas Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Low, Malcolm J.. Vollum Institute; Estados Unidos
Fil: Grandy, David K.. Oregon Health Science University; Estados Unidos
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Antonelli, Marta Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Materia
D4 Knockout Mice
Benzamides Binding
D2-Type Recptors
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:11336/39229
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/39229
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Quantitative analysis of the dopamine D4 receptor in the mouse brainDefagot, Maria CristinaFalzone, Tomas LuisLow, Malcolm J.Grandy, David K.Rubinstein, MarceloAntonelli, Marta CristinaD4 Knockout MiceBenzamides BindingD2-Type Recptorshttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3The D4 receptor (D4R), a member of the dopamine D2-like receptor family, has been implicated in the pathophysiology of several diseases and has been the target of various investigations regarding its distribution and quantification. The brain distribution of the D4R has been well described in various species, but the quantification is still an issue of controversy, because no specific ligand is commercially available. To circumvent this difficulty we have performed a biochemical and autoradiographical study in brain samples obtained from mice lacking D4Rs and their wild-type siblings; comparison of their binding parameters allows a more accurate quantification of the members of the D2-like receptor family (D2, D3, and D4 receptors). We found that the distribution of D2-like receptors in mouse brain is similar to that of rat brain, i.e., caudate putamen, nucleus accumbens, olfactory tubercle, and hippocampus. The contribution of the D4R to the overall population of D2-like receptors is 17% in nucleus accumbens, 21% in caudate putamen and olfactory tubercle, and 40% in hippocampus. Based on our study we conclude that nemonapride probably binds to nondopaminergic sites that if not properly blocked may lead to overestimations of D4R levels. We observed that the experimental condition that better estimates the density of D4 receptors is the displacement of D2 and D3 [3H]nemonapride binding sites with cold raclopride.Fil: Defagot, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Falzone, Tomas Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Low, Malcolm J.. Vollum Institute; Estados UnidosFil: Grandy, David K.. Oregon Health Science University; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Antonelli, Marta Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaWiley-liss, Div John Wiley & Sons Inc2000-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/39229Defagot, Maria Cristina; Falzone, Tomas Luis; Low, Malcolm J.; Grandy, David K.; Rubinstein, Marcelo; et al.; Quantitative analysis of the dopamine D4 receptor in the mouse brain; Wiley-liss, Div John Wiley & Sons Inc; Journal of Neuroscience Research; 59; 2; 1-2000; 202-2080360-4012CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/(SICI)1097-4547(20000115)59:2<202::AID-JNR6>3.0.CO;2-5info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/%28SICI%291097-4547%2820000115%2959%3A2%3C202%3A%3AAID-JNR6%3E3.0.CO%3B2-5info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:12:10Zoai:ri.conicet.gov.ar:11336/39229instacron: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:34982025-10-22 12:12:10.286CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Quantitative analysis of the dopamine D4 receptor in the mouse brain
title Quantitative analysis of the dopamine D4 receptor in the mouse brain
spellingShingle Quantitative analysis of the dopamine D4 receptor in the mouse brain
Defagot, Maria Cristina
D4 Knockout Mice
Benzamides Binding
D2-Type Recptors
title_short Quantitative analysis of the dopamine D4 receptor in the mouse brain
title_full Quantitative analysis of the dopamine D4 receptor in the mouse brain
title_fullStr Quantitative analysis of the dopamine D4 receptor in the mouse brain
title_full_unstemmed Quantitative analysis of the dopamine D4 receptor in the mouse brain
title_sort Quantitative analysis of the dopamine D4 receptor in the mouse brain
dc.creator.none.fl_str_mv Defagot, Maria Cristina
Falzone, Tomas Luis
Low, Malcolm J.
Grandy, David K.
Rubinstein, Marcelo
Antonelli, Marta Cristina
author Defagot, Maria Cristina
author_facet Defagot, Maria Cristina
Falzone, Tomas Luis
Low, Malcolm J.
Grandy, David K.
Rubinstein, Marcelo
Antonelli, Marta Cristina
author_role author
author2 Falzone, Tomas Luis
Low, Malcolm J.
Grandy, David K.
Rubinstein, Marcelo
Antonelli, Marta Cristina
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv D4 Knockout Mice
Benzamides Binding
D2-Type Recptors
topic D4 Knockout Mice
Benzamides Binding
D2-Type Recptors
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The D4 receptor (D4R), a member of the dopamine D2-like receptor family, has been implicated in the pathophysiology of several diseases and has been the target of various investigations regarding its distribution and quantification. The brain distribution of the D4R has been well described in various species, but the quantification is still an issue of controversy, because no specific ligand is commercially available. To circumvent this difficulty we have performed a biochemical and autoradiographical study in brain samples obtained from mice lacking D4Rs and their wild-type siblings; comparison of their binding parameters allows a more accurate quantification of the members of the D2-like receptor family (D2, D3, and D4 receptors). We found that the distribution of D2-like receptors in mouse brain is similar to that of rat brain, i.e., caudate putamen, nucleus accumbens, olfactory tubercle, and hippocampus. The contribution of the D4R to the overall population of D2-like receptors is 17% in nucleus accumbens, 21% in caudate putamen and olfactory tubercle, and 40% in hippocampus. Based on our study we conclude that nemonapride probably binds to nondopaminergic sites that if not properly blocked may lead to overestimations of D4R levels. We observed that the experimental condition that better estimates the density of D4 receptors is the displacement of D2 and D3 [3H]nemonapride binding sites with cold raclopride.
Fil: Defagot, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Falzone, Tomas Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Low, Malcolm J.. Vollum Institute; Estados Unidos
Fil: Grandy, David K.. Oregon Health Science University; Estados Unidos
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Antonelli, Marta Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
description The D4 receptor (D4R), a member of the dopamine D2-like receptor family, has been implicated in the pathophysiology of several diseases and has been the target of various investigations regarding its distribution and quantification. The brain distribution of the D4R has been well described in various species, but the quantification is still an issue of controversy, because no specific ligand is commercially available. To circumvent this difficulty we have performed a biochemical and autoradiographical study in brain samples obtained from mice lacking D4Rs and their wild-type siblings; comparison of their binding parameters allows a more accurate quantification of the members of the D2-like receptor family (D2, D3, and D4 receptors). We found that the distribution of D2-like receptors in mouse brain is similar to that of rat brain, i.e., caudate putamen, nucleus accumbens, olfactory tubercle, and hippocampus. The contribution of the D4R to the overall population of D2-like receptors is 17% in nucleus accumbens, 21% in caudate putamen and olfactory tubercle, and 40% in hippocampus. Based on our study we conclude that nemonapride probably binds to nondopaminergic sites that if not properly blocked may lead to overestimations of D4R levels. We observed that the experimental condition that better estimates the density of D4 receptors is the displacement of D2 and D3 [3H]nemonapride binding sites with cold raclopride.
publishDate 2000
dc.date.none.fl_str_mv 2000-01
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/11336/39229
Defagot, Maria Cristina; Falzone, Tomas Luis; Low, Malcolm J.; Grandy, David K.; Rubinstein, Marcelo; et al.; Quantitative analysis of the dopamine D4 receptor in the mouse brain; Wiley-liss, Div John Wiley & Sons Inc; Journal of Neuroscience Research; 59; 2; 1-2000; 202-208
0360-4012
CONICET Digital
CONICET
url http://hdl.handle.net/11336/39229
identifier_str_mv Defagot, Maria Cristina; Falzone, Tomas Luis; Low, Malcolm J.; Grandy, David K.; Rubinstein, Marcelo; et al.; Quantitative analysis of the dopamine D4 receptor in the mouse brain; Wiley-liss, Div John Wiley & Sons Inc; Journal of Neuroscience Research; 59; 2; 1-2000; 202-208
0360-4012
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/(SICI)1097-4547(20000115)59:2<202::AID-JNR6>3.0.CO;2-5
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/%28SICI%291097-4547%2820000115%2959%3A2%3C202%3A%3AAID-JNR6%3E3.0.CO%3B2-5
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley-liss, Div John Wiley & Sons Inc
publisher.none.fl_str_mv Wiley-liss, Div John Wiley & Sons Inc
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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