Substitution of a mutant alpha2a-adrenergic receptor via "hit and run" gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo.
Proc Natl Acad Sci U S A
; 94(18): 9950-5, 1997 Sep 02.
Article
en En
| MEDLINE
| ID: mdl-9275232
Norepinephrine contributes to antinociceptive, sedative, and sympatholytic responses in vivo, and alpha2 adrenergic receptor (alpha2AR) agonists are used clinically to mimic these effects. Lack of subtype-specific agonists has prevented elucidation of the role that each alpha2AR subtype (alpha2A, alpha2B, and alpha2C) plays in these central effects. Here we demonstrate that alpha2AR agonist-elicited sedative, anesthetic-sparing, and analgesic responses are lost in a mouse line expressing a subtly mutated alpha2AAR, D79N alpha2AAR, created by two-step homologous recombination. These functional changes are accompanied by failure of the D79N alpha2AAR to inhibit voltage-gated Ca2+ currents and spontaneous neuronal firing, a measure of K+ current activation. These results provide definitive evidence that the alpha2AAR subtype is the primary mediator of clinically important central actions of alpha2AR agonists and suggest that the D79N alpha2AAR mouse may serve as a model for exploring other possible alpha2AAR functions in vivo.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Conducta Animal
/
Receptores Adrenérgicos alfa 2
/
Analgésicos
/
Anestésicos
Límite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
1997
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos