Kim Yonjung, Park Myoung Kyu, Uhm Dae-Yong, Chung Sungkwon
Department of Physiology, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
Biochem Biophys Res Commun. 2007 Jul 6;358(3):796-801. doi: 10.1016/j.bbrc.2007.04.198. Epub 2007 May 8.
Corticotrophin-releasing factor (CRF) is the main regulator of the body's stress axis and its signal is translated through G-protein-coupled CRF receptors (CRF-R1, CRF-R2). Even though CRF receptors are present in the midbrain dopamine neurons, the cellular mechanism of CRF action is not clear yet. Since voltage-dependent Ca(2+) channels are highly expressed and important in dopamine neuronal functions, we tested the effect of CRF on voltage-dependent Ca(2+) channels in MN9D cells, a model of dopamine neurons. The application of CRF-related peptide, urocortin 1, reversibly inhibited T-type Ca(2+) currents, which was a major Ca(2+) channel in the cells. The effect of urocortin was abolished by specific CRF-R1 antagonist and was mimicked by protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate. PKC inhibitors abolished the effect of urocortin. These results suggest that urocortin modulates T-type Ca(2+) channel by interacting with CRF-R1 via the activation of PKC signal pathway in MN9D cells.
促肾上腺皮质激素释放因子（CRF）是机体应激轴的主要调节因子，其信号通过G蛋白偶联的CRF受体（CRF-R1、CRF-R2）进行传导。尽管CRF受体存在于中脑多巴胺神经元中，但CRF作用的细胞机制尚不清楚。由于电压依赖性Ca(2+)通道在多巴胺神经元功能中高度表达且具有重要作用，我们在MN9D细胞（一种多巴胺神经元模型）中测试了CRF对电压依赖性Ca(2+)通道的影响。应用CRF相关肽urocortin 1可可逆性抑制T型Ca(2+)电流，T型Ca(2+)电流是该细胞中的主要Ca(2+)通道。urocortin的作用被特异性CRF-R1拮抗剂消除，并被蛋白激酶C（PKC）激活剂佛波酯12-肉豆蔻酸酯13-乙酸酯模拟。PKC抑制剂消除了urocortin的作用。这些结果表明，urocortin通过在MN9D细胞中激活PKC信号通路与CRF-R1相互作用来调节T型Ca(2+)通道。
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