| RRC ID |
88430
|
| 著者 |
Zhang X, Nagai T, Ahammad RU, Kuroda K, Nakamuta S, Nakano T, Yukinawa N, Funahashi Y, Yamahashi Y, Amano M, Yoshimoto J, Yamada K, Kaibuchi K.
|
| タイトル |
Balance between dopamine and adenosine signals regulates the PKA/Rap1 pathway in striatal medium spiny neurons.
|
| ジャーナル |
Neurochem Int
|
| 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.
|
| 巻・号 |
122
|
| ページ |
8-18
|
| 公開日 |
2019-1-1
|
| DOI |
10.1016/j.neuint.2018.10.008
|
| PII |
S0197-0186(18)30290-0
|
| PMID |
30336179
|
| MeSH |
Adenosine / metabolism*
Animals
Corpus Striatum / metabolism*
Cyclic AMP-Dependent Protein Kinases / metabolism
Dopamine / metabolism*
Dopamine Agonists / pharmacology
Male
Mice, Inbred C57BL
Neurons / metabolism
Receptors, Dopamine D1 / metabolism
Signal Transduction*
rap1 GTP-Binding Proteins / metabolism
|
| IF |
3.881
|
| リソース情報 |
| 実験動物マウス |
RBRC02332
RBRC03111 |
