Protein kinase C beta regulates the D2-like dopamine autoreceptor.
Neuropharmacology
; 89: 335-41, 2015 Feb.
Article
en En
| MEDLINE
| ID: mdl-25446677
ABSTRACT
The focus of this study was the regulation of the D2-like dopamine autoreceptor (D2 autoreceptor) by protein kinase Cß, a member of the protein kinase C (PKC) family. Together with the dopamine transporter, the D2 autoreceptor regulates the level of extracellular dopamine and thus dopaminergic signaling. PKC regulates neuronal signaling via several mechanisms, including desensitizing autoreceptors to increase the release of several different neurotransmitters. Here, using both PKCß(-/-) mice and specific PKCß inhibitors, we demonstrated that a lack of PKCß activity enhanced the D2 autoreceptor-stimulated decrease in dopamine release following both chemical and electrical stimulations. Inhibition of PKCß increased surface localization of D2R in mouse striatal synaptosomes, which could underlie the greater sensitivity to quinpirole following inhibition of PKCß. PKCß(-/-) mice displayed greater sensitivity to the quinpirole-induced suppression of locomotor activity, demonstrating that the regulation of the D2 autoreceptor by PKCß is physiologically significant. Overall, we have found that PKCß downregulates the D2 autoreceptor, providing an additional layer of regulation for dopaminergic signaling. We propose that in the absence of PKCß activity, surface D2 autoreceptor localization and thus D2 autoreceptor signaling is increased, leading to less dopamine in the extracellular space and attenuated dopaminergic signaling.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Dopamina
/
Receptores de Dopamina D2
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Proteína Quinasa C beta
Límite:
Animals
Idioma:
En
Revista:
Neuropharmacology
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos