| RRC ID |
44319
|
| 著者 |
Ikeda E, Matsunaga N, Kakimoto K, Hamamura K, Hayashi A, Koyanagi S, Ohdo S.
|
| タイトル |
Molecular mechanism regulating 24-hour rhythm of dopamine D3 receptor expression in mouse ventral striatum.
|
| ジャーナル |
Mol Pharmacol
|
| Abstract |
The dopamine D3 receptor (DRD3) in the ventral striatum is thought to influence motivation and motor functions. Although the expression of DRD3 in the ventral striatum has been shown to exhibit 24-hour variations, the mechanisms underlying the variation remain obscure. Here, we demonstrated that molecular components of the circadian clock act as regulators that control the 24-hour variation in the expression of DRD3. The transcription of DRD3 was enhanced by the retinoic acid-related orphan receptor α (RORα), and its activation was inhibited by the orphan receptor REV-ERBα, an endogenous antagonist of RORα. The serum or dexamethasone-induced oscillation in the expression of DRD3 in cells was abrogated by the downregulation or overexpression of REV-ERBα, suggesting that REV-ERBα functions as a regulator of DRD3 oscillations in the cellular autonomous clock. Chromatin immunoprecipitation assays of the DRD3 promoter indicated that the binding of the REV-ERBα protein to the DRD3 promoter increased in the early dark phase. DRD3 protein expression varied with higher levels during the dark phase. Moreover, the effects of the DRD3 agonist 7-hydroxy-N,N-dipropyl-2-aminotetralin (7-OH-DPAT)-induced locomotor hypoactivity were significantly increased when DRD3 proteins were abundant. These results suggest that RORα and REV-ERBα consist of a reciprocating mechanism wherein RORα upregulates the expression of DRD3, whereas REV-ERBα periodically suppresses the expression at the time of day when REV-ERBα is abundant. Our present findings revealed that a molecular link between the circadian clock and the function of DRD3 in the ventral striatum acts as a modulator of the pharmacological actions of DRD3 agonists/antagonists.
|
| 巻・号 |
83(5)
|
| ページ |
959-67
|
| 公開日 |
2013-5-1
|
| DOI |
10.1124/mol.112.083535
|
| PII |
mol.112.083535
|
| PMID |
23429911
|
| MeSH |
Animals
Basal Ganglia / drug effects
Basal Ganglia / metabolism
Basal Ganglia / physiology*
Cell Line
Cell Line, Tumor
Chromatin Immunoprecipitation / methods
Circadian Rhythm / physiology*
Dexamethasone / pharmacology
Down-Regulation / drug effects
Mice
Motor Activity / drug effects
Motor Activity / genetics
NIH 3T3 Cells
Nuclear Receptor Subfamily 1, Group D, Member 1 / genetics
Nuclear Receptor Subfamily 1, Group D, Member 1 / metabolism
Nuclear Receptor Subfamily 1, Group F, Member 1 / genetics
Nuclear Receptor Subfamily 1, Group F, Member 1 / metabolism
Promoter Regions, Genetic / drug effects
RNA, Messenger / genetics
Receptors, Dopamine D3 / agonists
Receptors, Dopamine D3 / antagonists & inhibitors
Receptors, Dopamine D3 / biosynthesis*
Receptors, Dopamine D3 / genetics
Tetrahydronaphthalenes / pharmacology
Transcription, Genetic / drug effects
Up-Regulation / drug effects
|
| IF |
3.664
|
| 引用数 |
23
|
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
|
| リソース情報 |
| ヒト・動物細胞 |
C-1300N18(RCB2620) |
