Functional and pharmacological role of the dopamine D4 receptor and its polymorphic variants

Autores
Ferré, Sergi; Belcher, Annabelle M.; Bonaventura, Jordi; Quiroz, César; Sánchez Soto, Marta; Casadó Anguera, Verónica; Cai, Ning Sheng; Moreno, Estefanía; Boateng, Comfort A.; Keck, Thomas M.; Florán, Benjamín; Earley, Christopher J.; Ciruela, Francisco; Casadó, Vincet; Rubinstein, Marcelo; Volkow, Nora D.
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The functional and pharmacological significance of the dopamine D4 receptor (D4R) has remained the least well understood of all the dopamine receptor subtypes. Even more enigmatic has been the role of the very prevalent human DRD4 gene polymorphisms in the region that encodes the third intracellular loop of the receptor. The most common polymorphisms encode a D4R with 4 or 7 repeats of a proline-rich sequence of 16 amino acids (D4.4R and D4.7R). DRD4 polymorphisms have been associated with individual differences linked to impulse control-related neuropsychiatric disorders, with the most consistent associations established between the gene encoding D4.7R and attention-deficit hyperactivity disorder (ADHD) and substance use disorders. The function of D4R and its polymorphic variants is being revealed by addressing the role of receptor heteromerization and the relatively avidity of norepinephrine for D4R. We review the evidence conveying a significant and differential role of D4.4R and D4.7R in the dopaminergic and noradrenergic modulation of the frontal cortico-striatal pyramidal neuron, with implications for the moderation of constructs of impulsivity as personality traits. This differential role depends on their ability to confer different properties to adrenergic α2A receptor (α2AR)-D4R heteromers and dopamine D2 receptor (D2R)-D4R heteromers, preferentially localized in the perisomatic region of the frontal cortical pyramidal neuron and its striatal terminals, respectively. We also review the evidence to support the D4R as a therapeutic target for ADHD and other impulse-control disorders, as well as for restless legs syndrome.
Fil: Ferré, Sergi. National Institutes on Drug Abuse; Estados Unidos
Fil: Belcher, Annabelle M.. University of Maryland; Estados Unidos
Fil: Bonaventura, Jordi. National Institutes on Drug Abuse; Estados Unidos. Universidad de Barcelona; España
Fil: Quiroz, César. National Institutes on Drug Abuse; Estados Unidos
Fil: Sánchez Soto, Marta. National Institutes on Drug Abuse; Estados Unidos
Fil: Casadó Anguera, Verónica. Universidad de Barcelona; España
Fil: Cai, Ning Sheng. National Institutes on Drug Abuse; Estados Unidos
Fil: Moreno, Estefanía. Universidad de Barcelona; España
Fil: Boateng, Comfort A.. High Point University. Fred Wilson School of Pharmacy.; Estados Unidos
Fil: Keck, Thomas M.. Rowan University; Reino Unido
Fil: Florán, Benjamín. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzados; México
Fil: Earley, Christopher J.. University Johns Hopkins; Estados Unidos
Fil: Ciruela, Francisco. Universidad de Barcelona; España
Fil: Casadó, Vincet. Universidad de Barcelona; España
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: Volkow, Nora D.. National Institutes of Health; Estados Unidos
Materia
Drd4
DOPAMINE
RATÓN MUTANTE
ADHD
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/240776
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/240776
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Functional and pharmacological role of the dopamine D4 receptor and its polymorphic variantsFerré, SergiBelcher, Annabelle M.Bonaventura, JordiQuiroz, CésarSánchez Soto, MartaCasadó Anguera, VerónicaCai, Ning ShengMoreno, EstefaníaBoateng, Comfort A.Keck, Thomas M.Florán, BenjamínEarley, Christopher J.Ciruela, FranciscoCasadó, VincetRubinstein, MarceloVolkow, Nora D.Drd4DOPAMINERATÓN MUTANTEADHDhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The functional and pharmacological significance of the dopamine D4 receptor (D4R) has remained the least well understood of all the dopamine receptor subtypes. Even more enigmatic has been the role of the very prevalent human DRD4 gene polymorphisms in the region that encodes the third intracellular loop of the receptor. The most common polymorphisms encode a D4R with 4 or 7 repeats of a proline-rich sequence of 16 amino acids (D4.4R and D4.7R). DRD4 polymorphisms have been associated with individual differences linked to impulse control-related neuropsychiatric disorders, with the most consistent associations established between the gene encoding D4.7R and attention-deficit hyperactivity disorder (ADHD) and substance use disorders. The function of D4R and its polymorphic variants is being revealed by addressing the role of receptor heteromerization and the relatively avidity of norepinephrine for D4R. We review the evidence conveying a significant and differential role of D4.4R and D4.7R in the dopaminergic and noradrenergic modulation of the frontal cortico-striatal pyramidal neuron, with implications for the moderation of constructs of impulsivity as personality traits. This differential role depends on their ability to confer different properties to adrenergic α2A receptor (α2AR)-D4R heteromers and dopamine D2 receptor (D2R)-D4R heteromers, preferentially localized in the perisomatic region of the frontal cortical pyramidal neuron and its striatal terminals, respectively. We also review the evidence to support the D4R as a therapeutic target for ADHD and other impulse-control disorders, as well as for restless legs syndrome.Fil: Ferré, Sergi. National Institutes on Drug Abuse; Estados UnidosFil: Belcher, Annabelle M.. University of Maryland; Estados UnidosFil: Bonaventura, Jordi. National Institutes on Drug Abuse; Estados Unidos. Universidad de Barcelona; EspañaFil: Quiroz, César. National Institutes on Drug Abuse; Estados UnidosFil: Sánchez Soto, Marta. National Institutes on Drug Abuse; Estados UnidosFil: Casadó Anguera, Verónica. Universidad de Barcelona; EspañaFil: Cai, Ning Sheng. National Institutes on Drug Abuse; Estados UnidosFil: Moreno, Estefanía. Universidad de Barcelona; EspañaFil: Boateng, Comfort A.. High Point University. Fred Wilson School of Pharmacy.; Estados UnidosFil: Keck, Thomas M.. Rowan University; Reino UnidoFil: Florán, Benjamín. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzados; MéxicoFil: Earley, Christopher J.. University Johns Hopkins; Estados UnidosFil: Ciruela, Francisco. Universidad de Barcelona; EspañaFil: Casadó, Vincet. Universidad de Barcelona; EspañaFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Volkow, Nora D.. National Institutes of Health; Estados UnidosFrontiers Media2022-09-30info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/240776Ferré, Sergi; Belcher, Annabelle M.; Bonaventura, Jordi; Quiroz, César; Sánchez Soto, Marta; et al.; Functional and pharmacological role of the dopamine D4 receptor and its polymorphic variants; Frontiers Media; Frontiers in Endocrinology; 13; 30-9-2022; 1-141664-2392CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fendo.2022.1014678/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fendo.2022.1014678info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:15:13Zoai:ri.conicet.gov.ar:11336/240776instacron: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:34982025-09-10 13:15:13.985CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Functional and pharmacological role of the dopamine D4 receptor and its polymorphic variants
title Functional and pharmacological role of the dopamine D4 receptor and its polymorphic variants
spellingShingle Functional and pharmacological role of the dopamine D4 receptor and its polymorphic variants
Ferré, Sergi
Drd4
DOPAMINE
RATÓN MUTANTE
ADHD
title_short Functional and pharmacological role of the dopamine D4 receptor and its polymorphic variants
title_full Functional and pharmacological role of the dopamine D4 receptor and its polymorphic variants
title_fullStr Functional and pharmacological role of the dopamine D4 receptor and its polymorphic variants
title_full_unstemmed Functional and pharmacological role of the dopamine D4 receptor and its polymorphic variants
title_sort Functional and pharmacological role of the dopamine D4 receptor and its polymorphic variants
dc.creator.none.fl_str_mv Ferré, Sergi
Belcher, Annabelle M.
Bonaventura, Jordi
Quiroz, César
Sánchez Soto, Marta
Casadó Anguera, Verónica
Cai, Ning Sheng
Moreno, Estefanía
Boateng, Comfort A.
Keck, Thomas M.
Florán, Benjamín
Earley, Christopher J.
Ciruela, Francisco
Casadó, Vincet
Rubinstein, Marcelo
Volkow, Nora D.
author Ferré, Sergi
author_facet Ferré, Sergi
Belcher, Annabelle M.
Bonaventura, Jordi
Quiroz, César
Sánchez Soto, Marta
Casadó Anguera, Verónica
Cai, Ning Sheng
Moreno, Estefanía
Boateng, Comfort A.
Keck, Thomas M.
Florán, Benjamín
Earley, Christopher J.
Ciruela, Francisco
Casadó, Vincet
Rubinstein, Marcelo
Volkow, Nora D.
author_role author
author2 Belcher, Annabelle M.
Bonaventura, Jordi
Quiroz, César
Sánchez Soto, Marta
Casadó Anguera, Verónica
Cai, Ning Sheng
Moreno, Estefanía
Boateng, Comfort A.
Keck, Thomas M.
Florán, Benjamín
Earley, Christopher J.
Ciruela, Francisco
Casadó, Vincet
Rubinstein, Marcelo
Volkow, Nora D.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Drd4
DOPAMINE
RATÓN MUTANTE
ADHD
topic Drd4
DOPAMINE
RATÓN MUTANTE
ADHD
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The functional and pharmacological significance of the dopamine D4 receptor (D4R) has remained the least well understood of all the dopamine receptor subtypes. Even more enigmatic has been the role of the very prevalent human DRD4 gene polymorphisms in the region that encodes the third intracellular loop of the receptor. The most common polymorphisms encode a D4R with 4 or 7 repeats of a proline-rich sequence of 16 amino acids (D4.4R and D4.7R). DRD4 polymorphisms have been associated with individual differences linked to impulse control-related neuropsychiatric disorders, with the most consistent associations established between the gene encoding D4.7R and attention-deficit hyperactivity disorder (ADHD) and substance use disorders. The function of D4R and its polymorphic variants is being revealed by addressing the role of receptor heteromerization and the relatively avidity of norepinephrine for D4R. We review the evidence conveying a significant and differential role of D4.4R and D4.7R in the dopaminergic and noradrenergic modulation of the frontal cortico-striatal pyramidal neuron, with implications for the moderation of constructs of impulsivity as personality traits. This differential role depends on their ability to confer different properties to adrenergic α2A receptor (α2AR)-D4R heteromers and dopamine D2 receptor (D2R)-D4R heteromers, preferentially localized in the perisomatic region of the frontal cortical pyramidal neuron and its striatal terminals, respectively. We also review the evidence to support the D4R as a therapeutic target for ADHD and other impulse-control disorders, as well as for restless legs syndrome.
Fil: Ferré, Sergi. National Institutes on Drug Abuse; Estados Unidos
Fil: Belcher, Annabelle M.. University of Maryland; Estados Unidos
Fil: Bonaventura, Jordi. National Institutes on Drug Abuse; Estados Unidos. Universidad de Barcelona; España
Fil: Quiroz, César. National Institutes on Drug Abuse; Estados Unidos
Fil: Sánchez Soto, Marta. National Institutes on Drug Abuse; Estados Unidos
Fil: Casadó Anguera, Verónica. Universidad de Barcelona; España
Fil: Cai, Ning Sheng. National Institutes on Drug Abuse; Estados Unidos
Fil: Moreno, Estefanía. Universidad de Barcelona; España
Fil: Boateng, Comfort A.. High Point University. Fred Wilson School of Pharmacy.; Estados Unidos
Fil: Keck, Thomas M.. Rowan University; Reino Unido
Fil: Florán, Benjamín. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzados; México
Fil: Earley, Christopher J.. University Johns Hopkins; Estados Unidos
Fil: Ciruela, Francisco. Universidad de Barcelona; España
Fil: Casadó, Vincet. Universidad de Barcelona; España
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: Volkow, Nora D.. National Institutes of Health; Estados Unidos
description The functional and pharmacological significance of the dopamine D4 receptor (D4R) has remained the least well understood of all the dopamine receptor subtypes. Even more enigmatic has been the role of the very prevalent human DRD4 gene polymorphisms in the region that encodes the third intracellular loop of the receptor. The most common polymorphisms encode a D4R with 4 or 7 repeats of a proline-rich sequence of 16 amino acids (D4.4R and D4.7R). DRD4 polymorphisms have been associated with individual differences linked to impulse control-related neuropsychiatric disorders, with the most consistent associations established between the gene encoding D4.7R and attention-deficit hyperactivity disorder (ADHD) and substance use disorders. The function of D4R and its polymorphic variants is being revealed by addressing the role of receptor heteromerization and the relatively avidity of norepinephrine for D4R. We review the evidence conveying a significant and differential role of D4.4R and D4.7R in the dopaminergic and noradrenergic modulation of the frontal cortico-striatal pyramidal neuron, with implications for the moderation of constructs of impulsivity as personality traits. This differential role depends on their ability to confer different properties to adrenergic α2A receptor (α2AR)-D4R heteromers and dopamine D2 receptor (D2R)-D4R heteromers, preferentially localized in the perisomatic region of the frontal cortical pyramidal neuron and its striatal terminals, respectively. We also review the evidence to support the D4R as a therapeutic target for ADHD and other impulse-control disorders, as well as for restless legs syndrome.
publishDate 2022
dc.date.none.fl_str_mv 2022-09-30
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/11336/240776
Ferré, Sergi; Belcher, Annabelle M.; Bonaventura, Jordi; Quiroz, César; Sánchez Soto, Marta; et al.; Functional and pharmacological role of the dopamine D4 receptor and its polymorphic variants; Frontiers Media; Frontiers in Endocrinology; 13; 30-9-2022; 1-14
1664-2392
CONICET Digital
CONICET
url http://hdl.handle.net/11336/240776
identifier_str_mv Ferré, Sergi; Belcher, Annabelle M.; Bonaventura, Jordi; Quiroz, César; Sánchez Soto, Marta; et al.; Functional and pharmacological role of the dopamine D4 receptor and its polymorphic variants; Frontiers Media; Frontiers in Endocrinology; 13; 30-9-2022; 1-14
1664-2392
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.frontiersin.org/articles/10.3389/fendo.2022.1014678/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fendo.2022.1014678
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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 12.993085

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