Physiological exposure to melatonin supersensitizes the cyclic adenosine 3',5'-monophosphate-dependent signal transduction cascade in Chinese hamster ovary cells expressing the human mt1 melatonin receptor.

Physiological exposure to melatonin supersensitizes the cyclic adenosine 3',5'-monophosphate-dependent signal transduction cascade in Chinese hamster ovary cells expressing the human mt1 melatonin receptor.
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DOI:
10.1210/endo.139.7.6102
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发表时间:
1998-07
期刊:
影响因子:
4.8
通讯作者:
P. Witt‐Enderby;M. Masana;M. Dubocovich
P. Witt‐Enderby;M. Masana;M. Dubocovich
中科院分区:
医学2区
文献类型:
--
作者:
P. Witt‐Enderby;M. Masana;M. Dubocovich

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在这里,我们报道了短期接触褪黑素对中国仓鼠卵巢(CHO)细胞中人MT1(H MT1)褪黑素受体介导的信号转导的影响,以及类似于褪黑激素释放的生理模式对cAMP介导的信号转导的影响。将hMT1褪黑素受体短时间(10分钟)暴露于褪黑素(400 PM)可抑制Forsklin刺激的cAMP形成、cAMP依赖的蛋白激酶活性和cAMP反应元件结合蛋白的磷酸化。然而,用褪黑激素处理MT1-CHO细胞的方式与体内褪黑激素受体的激活方式非常相似(即400 PM褪黑素作用8小时以模拟黑暗),导致在撤退期间(即16小时不含褪黑素以模拟昼夜光周期的光周期)cAMP依赖的信号转导级联超敏。在戒断过程中,Forsklin诱导cAMP形成呈时间依赖性(1-16h)增加(∼为对照组的200%).
Here, we report the effects of short exposure to melatonin on the human mt1 (h mt1) melatonin receptor-mediated signaling in Chinese hamster ovary (CHO) cells, and the consequences of an exposure that resembles the physiological pattern of melatonin release on cAMP-mediated signal transduction. Short exposure (10 min) of h mt1 melatonin receptors to melatonin (400 pm) inhibited forskolin-stimulated cAMP formation, cAMP-dependent protein kinase activity, and phosphorylation of the cAMP response element-binding protein. However, treatment of mt1-CHO cells with melatonin in a manner that closely mimics the in vivo activation of melatonin receptors (i.e. 400 pm melatonin for 8 h to mimic darkness) resulted in a supersensitization of the cAMP-dependent signal transduction cascade during the period of withdrawal (i.e. 16 h without melatonin to mimic the light cycle of a diurnal photoperiod). During the period of withdrawal, forskolin induced a time-dependent (1–16 h) increase in cAMP formation (∼200% of control...