Second messenger mechanisms governing opiate peptide transmitter regulation in the rat adrenal medulla.
Second messenger mechanisms governing opiate peptide transmitter regulation in the rat adrenal medulla.
复制标题
控制大鼠肾上腺髓质阿片肽递质调节的第二信使机制。
DOI：
10.1016/0006-8993(88)91407-2
复制
发表时间：
1988
期刊：
影响因子：
2.9
通讯作者：
Black,IB
中科院分区：
文献类型：
--
作者：
LaGamma,EF;White,JD;McKelvy,JF;Black,IB
通过手术肾上腺去神经支配或通过髓质切除减少跨突触活动，增加Leu-Enk免疫反应性（Leu-Enk）和前脑啡肽原mRNA（prepro-EK）。膜去极化阻止这种上升。为了确定去极化效应是否由钙离子的细胞内运动介导，在EGTA或钙离子“通道”阻断剂D 600或维拉帕米存在下，对延髓进行去极化。抑制Ca ~（2+）内流阻止KCl诱导的去极化对Leu-Enk和prepro-EK升高的影响。增加细胞内钙离子与离子载体A23187，在去极化剂的情况下，再现去极化的效果。相比之下，髓质生长在A23187的存在下，但在无钙培养基中，表现出类似的增加prepro-EK mRNA和Leu-Enk，表明对钙的绝对需求。此外，KCl的抑制作用可以部分阻断钙调蛋白和蛋白激酶C拮抗剂，三氟拉嗪。然而，KCl的影响没有拮抗的优惠钙调蛋白抑制剂W7，W13或calmidizolium，即使在剂量比所需的10倍，以防止钙调蛋白依赖性的影响。因此，这些数据表明，肾上腺脑啡肽的跨突触活性和膜去极化的抑制作用发生通过Ca 2+，也许通过蛋白激酶-C依赖的途径，已知的机制，增加儿茶酚胺的生物合成。那么似乎相同或相似的分子机制可以导致这些共定位递质系统的差异调节。
Decreasing transsynaptic activity through surgical adrenal denervation or by medullary explantation, increases Leu-enkephalin immunoreactivity (Leu-Enk) and preproenkephalin mRNA (prepro-EK). Membrane depolarization prevents this rise. To determine whether depolarizing effects are mediated by intracellular movement of calcium ions, explanted medullae were depolarized in the presence of EGTA or the calcium ion ‘channel’ blockers D600 or verapamil. Inhibition of Ca2+influx prevented the effects of KCl-induced depolarization on the rise in Leu-Enk and on prepro-EK. Increasing intracellular Ca2+with the ionophore A23187, in the absence of depolarizing agents, reproduced the effects of depolarization. By contrast, medullae grown in the presence of A23187, but in Ca2+-free medium, showed similar increases in prepro-EK mRNA and Leu-Enk, indicating an absolute requirement for Ca2+. In addition, KCl-inhibitory effects could be partially blocked by the calmodulin and protein kinase-C antagonist, trifluoperazine. However, KCl effects were not antagonized by the preferential calmodulin inhibitors W7, W13 or calmidizolium even at doses 10-fold higher than required to prevent calmodulin-dependent effects. Thus, these data suggest that inhibitory effects of transsynaptic activity and membrane depolarization on adrenal enkephalin occurs through Ca2+and perhaps through a protein kinase-C dependent pathway, mechanisms known to augment catecholamine biosynthesis. It appears then that the same or similar molecular mechanisms can result in differential regulation of these co-localized transmitter systems.