Repositorio Institucional
Repositorio Institucional
CONICET Digital
  • Inicio
  • EXPLORAR
    • AUTORES
    • DISCIPLINAS
    • COMUNIDADES
  • Estadísticas
  • Novedades
    • Noticias
    • Boletines
  • Ayuda
    • General
    • Datos de investigación
  • Acerca de
    • CONICET Digital
    • Equipo
    • Red Federal
  • Contacto
JavaScript is disabled for your browser. Some features of this site may not work without it.
  • INFORMACIÓN GENERAL
  • RESUMEN
  • ESTADISTICAS
 
Artículo

Differential Pharmacological Activity of JN403 between á7 and Muscle Nicotinic Acetylcholine Receptors

Arias, Hugo Ruben; de Rosa, Maria JoseIcon ; Bergé, IgnacioIcon ; Feuerbach, Dominik; Bouzat, Cecilia BeatrizIcon
Fecha de publicación: 10/2013
Editorial: American Chemical Society
Revista: Biochemistry
ISSN: 0006-2960
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Farmacología y Farmacia

Resumen

The differential action of the novel agonist JN403 at neuronalα7 and muscle nicotinic receptors (AChRs)was explored by using a combination of functional and structural approaches. Single-channel recordings reveal that JN403 is a potent agonist of α7 but a very low-efficacy agonist of muscle AChRs. JN403 elicits detectable openings of α7 and muscle AChRs at concentrations∼1000-fold lower and∼20-fold higher, respectively, than that for ACh. Single-channel activity elicited by JN403 is very similar to that elicited by ACh in α7 but profoundly different in muscle AChRs, where openings are brief and infrequent and do not appear in clusters at any concentration. JN403 elicits single-channel activity of muscle AChRs lacking theεsubunit, with opening events being more frequent and prolonged than those of wild-type AChRs. This finding is in line with the molecular docking studies predicting that JN403 may form a hydrogen bond required for potent activation at the α−δ but not at the α−ε binding site. JN403 does not elicit detectable Ca2+ influx in muscle AChRs but inhibits (±)-epibatidine-elicited influx mainly by a noncompetitive mechanism. Such inhibition is compatible with single-channel recordings revealing that JN403 produces open-channel blockade and early termination of ACh-elicited clusters, and it is therefore also a potent desensitizing enhancer of muscle AChRs. The latter mechanism is supported by the JN403-induced increase in the level of binding of [3H]cytisine and [3H]TCP to resting AChRs. Elucidation of the differences in activity of JN403 between neuronal α7 and muscle AChRs provides further insights into mechanisms underlying selectivity for α7 AChRs.
Palabras clave: Receptor Nicotinico , Agonista , Patch Clamp , Receptor Cys-Loop
Ver el registro completo
 
Archivos asociados
Thumbnail
 
Tamaño: 2.846Mb
Formato: PDF
.
Descargar
Licencia
info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)
Identificadores
URI: http://hdl.handle.net/11336/4538
DOI: http://dx.doi.org/ 10.1021/bi4012572
URL: http://www.ncbi.nlm.nih.gov/pubmed/24164482
DOI: http://dx.doi.org/10.1021/bi4012572
Colecciones
Articulos(INIBIBB)
Articulos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Citación
Arias, Hugo Ruben; de Rosa, Maria Jose; Bergé, Ignacio; Feuerbach, Dominik; Bouzat, Cecilia Beatriz; Differential Pharmacological Activity of JN403 between á7 and Muscle Nicotinic Acetylcholine Receptors; American Chemical Society; Biochemistry; 52; 10-2013; 8480-8488
Compartir
Altmétricas
 

Enviar por e-mail
Separar cada destinatario (hasta 5) con punto y coma.
  • Facebook
  • X Conicet Digital
  • Instagram
  • YouTube
  • Sound Cloud
  • LinkedIn

Los contenidos del CONICET están licenciados bajo Creative Commons Reconocimiento 2.5 Argentina License

https://www.conicet.gov.ar/ - CONICET

Inicio

Explorar

  • Autores
  • Disciplinas
  • Comunidades

Estadísticas

Novedades

  • Noticias
  • Boletines

Ayuda

Acerca de

  • CONICET Digital
  • Equipo
  • Red Federal

Contacto

Godoy Cruz 2290 (C1425FQB) CABA – República Argentina – Tel: +5411 4899-5400 repositorio@conicet.gov.ar
TÉRMINOS Y CONDICIONES