Balance between dopamine and adenosine signals regulates the PKA/Rap1 pathway in striatal medium spiny neurons. (January 2019)

• Record Type: Journal Article
• Authors: Zhang, Xinjian; Nagai, Taku; Ahammad, Rijwan Uddin; Kuroda, Keisuke; Nakamuta, Shinichi; Nakano, Takashi; Yukinawa, Naoto; Funahashi, Yasuhiro; Yamahashi, Yukie; Amano, Mutsuki; Yoshimoto, Junichiro; Yamada, Kiyofumi; Kaibuchi, Kozo
• Is Part Of: Neurochemistry international. Volume 122(2019)
• Page Start: 8
• Page End: 18
• Publication Date: 2019-01
• Subjects: Dopamine -- Adenosine -- Striatum -- Medium spiny neuron -- PKA -- Rap1gap; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2018.10.008
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: Medium spiny neurons (MSNs) expressing dopamine D1 receptor (D1R) or D2 receptor (D2R) are major components of the striatum. Stimulation of D1R activates protein kinase A (PKA) through Golf to increase neuronal activity, while D2R stimulation inhibits PKA through Gi . Adenosine A2A receptor (A2AR) coupled to Golf is highly expressed in D2R-MSNs within the striatum. However, how dopamine and adenosine co-operatively regulate PKA activity remains largely unknown. Here, we measured Rap1gap serine 563 phosphorylation to monitor PKA activity and examined dopamine and adenosine signals in MSNs. We found that a D1R agonist increased Rap1gap phosphorylation in striatal slices and in D1R-MSNs in vivo . A2AR agonist CGS21680 increased Rap1gap phosphorylation, and pretreatment with the D2R agonist quinpirole blocked this effect in striatal slices. D2R antagonist eticlopride increased Rap1gap phosphorylation in D2R-MSNs in vivo, and the effect of eticlopride was blocked by the pretreatment with the A2AR antagonist SCH58261. These results suggest that adenosine positively regulates PKA in D2R-MSNs through A2AR, while this effect is blocked by basal dopamine in vivo . Incorporating computational model analysis, we propose that the shift from D1R-MSNs to D2R-MSNs or vice versa appears to depend predominantly on a change in dopamine concentration. Graphical abstract: Highlights: D1R agonist enhanced PKA-mediated Rap1gap phosphorylation in vitro and in vivo . A2AR agonist enhanced PKA-mediated Rap1gap phosphorylation in vitro . D2R antagonist enhanced PKA-mediated Rap1gap phosphorylation in vivo . Effect of D2R antagonist was blocked by pretreatment with A2AR antagonist in vivo .