Protein kinase C beta regulates the D-2-Like dopamine autoreceptor

作者：Luderman Kathryn D; Chen Rong; Ferris Mark J; Jones Sara R; Gnegy Margaret E^*

来源：Neuropharmacology, 2015, 89: 335-341.

DOI：10.1016/j.neuropharm.2014.10.012

• Dopamine
• Autoreceptor
• Exocytosis
• Quinpirole
• Synaptosomes

The focus of this study was the regulation of the D-2-like dopamine autoreceptor (D-2 autoreceptor) by protein kinase C beta, a member of the protein kinase C (PKC) family. Together with the dopamine transporter, the D-2 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 PKC beta(-/-) mice and specific PKCO inhibitors, we demonstrated that a lack of PKCO activity enhanced the D-2 autoreceptor-stimulated decrease in dopamine release following both chemical and electrical stimulations. Inhibition of PKCO increased surface localization of D2R in mouse striatal synaptosomes, which could underlie the greater sensitivity to quinpirole following inhibition of PKC beta. PKC beta(-/-) mice displayed greater sensitivity to the quinpirole-induced suppression of locomotor activity, demonstrating that the regulation of the D-2 autoreceptor by PKC beta is physiologically significant. Overall, we have found that PKC beta downregulates the D-2 autoreceptor, providing an additional layer of regulation for dopaminergic signaling. We propose that in the absence of PKC beta activity, surface D-2 autoreceptor localization and thus D-2 autoreceptor signaling is increased, leading to less dopamine in the extracellular space and attenuated dopaminergic signaling.

• 出版日期2015-2