Pharmacology of signaling induced by dopamine D(1)-like receptor activation.
Pharmacology of signaling induced by dopamine D(1)-like receptor activation.
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DOI：
10.1016/j.pharmthera.2010.05.003
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发表时间：
2010-10
影响因子：
13.5
通讯作者：
Undieh, Ashiwel S.
中科院分区：
文献类型：
--
作者：
Undieh, Ashiwel S.
关键词：
多巴胺D1样受体由D1和D5亚型组成，与基本神经生理过程（如情绪、动机、认知功能和运动活动）的多巴胺能调节密切相关。受到刺激后，d1样受体启动通过腺苷酸环化酶或磷酸肌肽代谢介导的信号转导级联反应，随后增强多个下游激酶级联反应。后一种作用传播并进一步放大受体信号，从而使d1样受体易于与各种其他介质和受体系统进行多方面的相互作用。腺苷酸环化酶对多巴胺或选择性D1样受体激动剂的反应可靠地与D1亚型相关，而新出现的证据表明，天然脑组织中的磷酸肌苷反应可能优先通过刺激D5受体介导。除了每种受体亚型与特定G蛋白的经典偶联外，还提出了其他生物物理模型，试图解释不同的亚细胞分布、异分子寡聚化和受体的活性依赖选择性。目前和未来的研究旨在揭示D5偶联到磷酸肌肽信号的分子机制、可能增强D5与D1亚型的药理学选择性的结构特征、多巴胺调节磷酸肌肽合成的机制，这些都有望在对多巴胺神经生物学的理解方面取得重大进展。各种响应性信号介质对D1或D5与d2样受体相互作用的贡献，以及可能归因于每种受体亚型和信号通路的多巴胺能功能谱。
Dopamine D1-like receptors consisting of D1 and D5 subtypes are intimately implicated in dopaminergic regulation of fundamental neurophysiologic processes such as mood, motivation, cognitive function, and motor activity. Upon stimulation, D1-like receptors initiate signal transduction cascades that are mediated through adenylyl cyclase or phosphoinositide metabolism, with subsequent enhancement of multiple downstream kinase cascades. The latter actions propagate and further amplify the receptor signals, thus predisposing D1-like receptors to multifaceted interactions with various other mediators and receptor systems. The adenylyl cyclase response to dopamine or selective D1-like receptor agonists is reliably associated with the D1 subtype, while emerging evidence indicates that the phosphoinositide responses in native brain tissues may be preferentially mediated through stimulation of the D5 receptor. Besides classic coupling of each receptor subtype to specific G proteins, additional biophysical models are advanced in attempts to account for differential subcellular distribution, heteromolecular oligomerization, and activity-dependent selectivity of the receptors. It is expected that significant advances in understanding of dopamine neurobiology will emerge from current and anticipated studies directed at uncovering the molecular mechanisms of D5 coupling to phosphoinositide signaling, the structural features that might enhance pharmacological selectivity for D5 versus D1 subtypes, the mechanism by which dopamine may modulate phosphoinositide synthesis, the contributions of the various responsive signal mediators to D1 or D5 interactions with D2-like receptors, and the spectrum of dopaminergic functions that may be attributed to each receptor subtype and signaling pathway.
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影响因子：
3.3
作者：
BESSON, MJ;GRAYBIEL, AM;NASTUK, MA
通讯作者：
NASTUK, MA
影响因子：
5
作者：
ARNT, J;HYTTEL, J;SANCHEZ, C
通讯作者：
SANCHEZ, C
影响因子：
5
作者：
Andringa, G;Drukarch, B;Stoof, JC
通讯作者：
Stoof, JC
影响因子：
2.3
作者：
Arias-Montano, J. -A.;Floran, B.;Young, J. M.
通讯作者：
Young, J. M.
DOI：
10.1016/0922-4106(90)90194-3
发表时间：
1990-06-12
期刊：
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION
影响因子：
--
作者：
ANDERSEN, PH;JANSEN, JA
通讯作者：
JANSEN, JA