Your browser doesn't support javascript.
loading
Gs- versus Golf-dependent functional selectivity mediated by the dopamine D1 receptor.
Yano, Hideaki; Cai, Ning-Sheng; Xu, Min; Verma, Ravi Kumar; Rea, William; Hoffman, Alexander F; Shi, Lei; Javitch, Jonathan A; Bonci, Antonello; Ferré, Sergi.
Afiliación
  • Yano H; National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA. hideaki.yano@nih.gov.
  • Cai NS; National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.
  • Xu M; National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.
  • Verma RK; National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.
  • Rea W; National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.
  • Hoffman AF; National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.
  • Shi L; National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.
  • Javitch JA; Department of Psychiatry, College of Physicians & Surgeons, Columbia University, New York, NY, 10032, USA.
  • Bonci A; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, 10032, USA.
  • Ferré S; National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.
Nat Commun ; 9(1): 486, 2018 02 05.
Article en En | MEDLINE | ID: mdl-29402888
The two highly homologous subtypes of stimulatory G proteins Gαs (Gs) and Gαolf (Golf) display contrasting expression patterns in the brain. Golf is predominant in the striatum, while Gs is predominant in the cortex. Yet, little is known about their functional distinctions. The dopamine D1 receptor (D1R) couples to Gs/olf and is highly expressed in cortical and striatal areas, making it an important therapeutic target for neuropsychiatric disorders. Using novel drug screening methods that allow analysis of specific G-protein subtype coupling, we found that, relative to dopamine, dihydrexidine and N-propyl-apomorphine behave as full D1R agonists when coupled to Gs, but as partial D1R agonists when coupled to Golf. The Gs/Golf-dependent biased agonism by dihydrexidine was consistently observed at the levels of cellular signaling, neuronal function, and behavior. Our findings of Gs/Golf-dependent functional selectivity in D1R ligands open a new avenue for the treatment of cortex-specific or striatum-specific neuropsychiatric dysfunction.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenantridinas / Receptores de Dopamina D1 / Subunidades alfa de la Proteína de Unión al GTP Gs / Subunidades alfa de la Proteína de Unión al GTP Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenantridinas / Receptores de Dopamina D1 / Subunidades alfa de la Proteína de Unión al GTP Gs / Subunidades alfa de la Proteína de Unión al GTP Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido