D1/D5 dopamine receptors stimulate intracellular calcium release in primary cultures of neocortical and hippocampal neurons
D1/D5 dopamine receptors stimulate intracellular calcium release in primary cultures of neocortical and hippocampal neurons
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DOI：
10.1152/jn.00541.2001
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发表时间：
2002-04-01
影响因子：
2.5
通讯作者：
Bergson, C
中科院分区：
文献类型：
--
作者：
Lezcano, N;Bergson, C
基底神经节、海马和大脑皮层中的D1/D5多巴胺受体调节运动、奖励和认知行为。先前的重组蛋白研究表明，在异源G（q/11）偶联G蛋白偶联受体（GPCR）激动剂引发的细胞中，当与钙蛋白共表达时，典型的G（s）连接的D1/D5受体可以刺激钙从内部储存中的强烈释放。为了了解更多关于这些D1/D5受体调节行为的细胞内信号传导机制，我们探索了内源性受体刺激神经元内钙释放的可能性。我们已经在海马和新皮层的原代培养物中鉴定了一群神经元，它们对D1/D5多巴胺受体激动剂有反应，细胞内钙（Ca-1（2+））水平显著增加。D1/D5受体刺激反应发生在细胞外Ca 2+不存在的情况下，表明Ca-1（2+）的升高涉及内部储存的释放。此外，D1/D5受体拮抗剂阻断反应。此外，D1/D5激动剂诱发的反应是状态依赖性的，需要用G（q/11）-偶联谷氨酸、5-羟色胺、毒蕈碱和肾上腺素能受体的激动剂或用高外部K+溶液引发。与此相反，D1/D5受体激动剂诱发的Ca 2+反应未检测到来自纹状体的神经元。然而，D1/D5激动剂提高cAMP水平在纹状体文化有效的新皮层和海马文化。此外，引发后的毛喉素和8-Br-cAMP刺激都不能模拟D1/D5激动剂诱发的新皮层神经元中的Ca 2+反应，表明增加的cAMP水平不足以刺激Ca 1（2+）释放。我们的数据表明，D1样多巴胺受体可能通过Ca 2+以及cAMP依赖性信号调节新皮层和海马神经元的兴奋性和突触功能。
D1/D5 dopamine receptors in basal ganglia, hippocampus, and cerebral cortex modulate motor, reward, and cognitive behavior. Previous work with recombinant proteins revealed that in cells primed with heterologous G(q/11)-coupled G-protein-coupled receptor (GPCR) agonists, the typically G(s)-linked D1/D5 receptors can stimulate robust release of calcium from internal stores when coexpressed with calcyon. To learn more about the intracellular signaling mechanisms underlying these D1/D5 receptor regulated behaviors, we explored the possibility that endogenous receptors stimulate internal release of calcium in neurons. We have identified a population of neurons in primary cultures of hippocampus and neocortex that respond to D1/D5 dopamine receptor agonists with a marked increase in intracellular calcium (Ca-i(2+)) levels. The D1/D5 receptor stimulated responses occurred in the absence of extracellular Ca2+ indicating the rises in Ca-i(2+) involve release from internal stores. In addition, the responses were blocked by D1/D5 receptor antagonists. Further, the D1/D5 agonist-evoked responses were state dependent, requiring priming with agonists of G(q/11)-coupled glutamate, serotonin, muscarinic, and adrenergic receptors or with high external K+ solution. In contrast, D1/D5 receptor agonist-evoked Ca2+ responses were not detected in neurons derived from striatum. However, D1/D5 agonists elevated cAMP levels in striatal cultures as effectively as in neocortical and hippocampal cultures. Further, neither forskolin nor 8-Br-cAMP stimulation following priming was able to mimic the D1/D5 agonist-evoked Ca2+ response in neocortical neurons indicating that increased cAMP levels are not sufficient to stimulate Ca-i(2+) release. Our data suggest that D1-like dopamine receptors likely modulate neocortical and hippocampal neuronal excitability and synaptic function via Ca2+ as well as cAMP-dependent signaling.