Neurotransmitter-induced inhibition of exocytosis in insulin-secreting beta cells by activation of calcineurin
Neurotransmitter-induced inhibition of exocytosis in insulin-secreting beta cells by activation of calcineurin
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DOI：
10.1016/s0896-6273(00)80183-x
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发表时间：
1996-09-01
期刊：
影响因子：
16.2
通讯作者：
Rorsman, P
中科院分区：
文献类型：
--
作者：
Renstrom, E;Ding, WG;Rorsman, P
神经递质和激素如生长抑素、甘丙肽和肾上腺素减少胰岛素分泌。它们的抑制作用包括直接干扰胞吐机制。我们已经研究了这种效应的分子过程，使用高分辨率的测量细胞电容。在不完全抑制葡萄糖刺激的电活动的浓度下，胞吐的抑制作用最大。该作用依赖于G蛋白的激活，但与电压依赖性Ca 2+电流或腺苷酸环化酶活性的抑制无关。由激动剂引发的分子过程最终导致Ca2+依赖性蛋白磷酸酶钙调神经磷酸酶的激活，并且抑制该酶的活性废除了它们对胞吐作用的作用。我们建议，机制类似于我们在这里报告可能有助于肾上腺素能和肽能抑制其他神经内分泌细胞和神经末梢的分泌。
Neurotransmitters and hormones such as somatostatin, galanin, and adrenalin reduce insulin secretion. Their inhibitory action involves direct interference with the exocytotic machinery. We have examined the molecular processes underlying this effect using high resolution measurements of cell capacitance. Suppression of exocytosis was maximal at concentrations that did not cause complete inhibition of glucose-stimulated electrical activity. This action was dependent on activation of G proteins but was not associated with inhibition of the voltage-dependent Ca2+ currents or adenylate cyclase activity. The molecular processes initiated by the agonists culminate in the activation of the Ca2+-dependent protein phosphatase calcineurin, and suppression of the activity of this enzyme abolishes their action on exocytosis. We propose that mechanisms similar to those we report here may contribute to adrenergic and peptidergic inhibition of secretion in other neuroendocrine cells and in nerve terminals.