Regulation by insulin of a unique neuronal Ca2+ pool and of neuropeptide secretion
Regulation by insulin of a unique neuronal Ca2+ pool and of neuropeptide secretion
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DOI：
10.1038/385343a0
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发表时间：
1997-01-23
期刊：
影响因子：
64.8
通讯作者：
Karzmarek, LK
中科院分区：
文献类型：
--
作者：
Jonas, EA;Knox, RJ;Karzmarek, LK
胰岛素受体是一种酪氨酸激酶受体，存在于哺乳动物脑中（1），在厌食症的袋细胞神经元中浓度较高（2）。我们在这里表明，胰岛素引起这些神经元细胞内Ca 2+浓度（[Ca 2 +]（i））的急剧上升，并触发神经肽的释放。胰岛素敏感的细胞内Ca 2+池与先前描述的对三磷酸肌醇敏感的Ca 2+储存和线粒体Ca 2+储存不同（3-7）。胰岛素而不是毒胡萝卜素刺激神经突远端的Ca 2+释放，这是神经肽分泌的假定位点（8，9）。胰岛素对细胞内Ca 2+释放和神经肽分泌的影响在不触发自发动作电位的情况下发生。在暴露于环AMP类似物后，[Ca 2 +]（i）的胰岛素敏感性升高移动到神经突的远端，这是一种导致神经元囊泡类似移位的治疗（10-12）。我们的数据表明，从一个不同的细胞内池与分泌囊泡的Ca 2+释放可能有助于神经肽的分泌，在神经元放电的情况下。
The insulin receptor is a tyrosine kinase receptor that is found in mammalian brain(1) and at high concentrations in the bag cell neurons of Aplysia(2). We show here that insulin causes an acute rise in intracellular Ca2+ concentration ([Ca2+](i)) in these neurons and triggers release of neuropeptide. The insulin-sensitive intracellular Ca2+ pool differs pharmacologically from previously described Ca2+ stores that are sensitive to inositol trisphosphate and from mitochondrial Ca2+ stores(3-7). Insulin, but not thapsigargin, stimulates Ca2+ release at the distal tips of neurites, the presumed site of neuropeptide secretion(8,9). The effects of insulin on intracellular Ca2+ release and neuropeptide secretion occur without triggering spontaneous action potentials. The insulin-sensitive rise in [Ca2+](i) moves into the distal tips of neurites after exposure to a cyclic AMP analogue, a treatment that causes a similar translocation of neuronal vesicles(10-12). Our data indicate that Ca2+ release from a distinct intracellular pool associated with secretory vesicles may contribute to secretion of neuropeptide in the absence of neuronal discharge.