Hartter D E, Barnea A
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas 75235.
Synapse. 1988;2(4):412-5. doi: 10.1002/syn.890020408.
The potential importance of copper (Cu) in neurosecretion can be inferred from the demonstration that extracellular Cu modulates the secretory function of peptidergic neurons (in vitro studies) and from the presence of high Cu concentrations in nerve terminals and secretory vesicles, primarily within the soluble matrix of the latter. We have previously hypothesized that vesicular Cu is released from neurons undergoing exocytosis and that such extracellular Cu plays an important modulatory role in the central nervous system. To test this Cu release hypothesis, rat hypothalami were incubated under in vitro conditions for 1 or 2 hr with 20 nM radiolabeled Cu (67Cu), and then 67Cu release was stimulated by a depolarizing concentration (60 mM) of K+. K+ markedly (P less than 0.001) stimulated 67Cu release in a Ca2+-dependent manner (stimulated release was 95 fmol/10 min/mg protein after 1 hr 67Cu loading and 160 after 2 hr). These amounts of released 67Cu account for about 10% of the total 67Cu taken up by the tissue. These results indicate that part of the 67Cu taken up by hypothalamic explants is directed into an intracellular compartment from where it can be released by a Ca2+-dependent mechanism, thus providing strong support to our hypothesis that release of copper is operative in situ in the brain.
铜（Cu）在神经分泌中的潜在重要性可以从以下方面推断得出：细胞外铜调节肽能神经元的分泌功能（体外研究），以及神经末梢和分泌小泡中存在高浓度的铜，主要存在于后者的可溶性基质中。我们之前曾假设，囊泡铜是从经历胞吐作用的神经元中释放出来的，并且这种细胞外铜在中枢神经系统中起重要的调节作用。为了验证这一铜释放假说，将大鼠下丘脑在体外条件下用20 nM放射性标记铜（67Cu）孵育1或2小时，然后用去极化浓度（60 mM）的钾离子刺激67Cu释放。钾离子以钙依赖的方式显著刺激67Cu释放（P小于0.001）（67Cu加载1小时后刺激释放为95 fmol/10分钟/毫克蛋白质，2小时后为160）。这些释放的67Cu量约占组织摄取的总67Cu的10%。这些结果表明，下丘脑外植体摄取的部分67Cu被导向细胞内区室，从那里它可以通过钙依赖机制释放，从而为我们的假说提供了有力支持，即铜的释放在大脑中是原位起作用的。
