P2X7 receptors in neurohypophysial terminals: evidence for their role in arginine-vasopressin secretion.
P2X7 receptors in neurohypophysial terminals: evidence for their role in arginine-vasopressin secretion.
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DOI：
10.1002/jcp.24453
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发表时间：
2014-03
影响因子：
5.6
通讯作者：
Lemos JR
中科院分区：
文献类型：
--
作者：
Cuadra AE;Custer EE;Bosworth EL;Lemos JR
精氨酸加压素（AVP）在维持心血管功能和相关病理中起主要作用。其释放进入循环的机制是复杂的，受到高度管制。最近的研究表明，嘌呤能受体P2 X7 R参与了大鼠下丘脑-神经垂体（NH）系统中儿茶酚胺增强AVP释放的作用。然而，P2 X7 R在该内分泌系统中的作用位点以及它是否直接介导分泌神经元中的释放尚未确定。我们假设P2 X7 R在NH末端表达并介导AVP释放。P2 X7 R功能首先通过在分离的NH末端中的膜片钳记录来检查。结果表明，孤立的终端的亚群显示高ATP敏感性或低ATP敏感性，后者是大鼠P2 X7 R的特征。另外的记录显示，显示对P2 X7 R选择性激动剂BzATP敏感的终末被P2 X7 R选择性拮抗剂AZ 10606120和亮蓝G进一步抑制。在共聚焦显微照片从孤立的终端的NH表明，P2 X7 R-免疫反应性定位于质膜。最后，检测P2 X7 R在AVP释放中的作用。我们的结果表明，BzATP诱发持续的AVP释放的NH端，这是由AZ 10606120抑制。综上所述，我们的数据使我们得出结论，P2 X7 R在NH末端表达，并证实其在AVP分泌中的作用。
Arginine-vasopressin (AVP) plays a major role in maintaining cardiovascular function and related pathologies. The mechanism involved in its release into the circulation is complex and highly regulated. Recent work has implicated the purinergic receptor, P2X7R, in a role for catecholamine-enhanced AVP release in the rat hypothalamic-neurohypophysial (NH) system. However, the site of P2X7R action in this endocrine system and whether or not it directly mediates release in secretory neurons have not been determined. We hypothesized that the P2X7R is expressed and mediates AVP release in NH terminals. P2X7R function was first examined by patch-clamp recordings in isolated NH terminals. Results revealed that subpopulations of isolated terminals displayed either high ATP-sensitivity or low ATP-sensitivity, the latter of which was characteristic of the rat P2X7R. Additional recordings showed that terminals showing sensitivity to the P2X7R-selective agonist, BzATP, were further inhibited by P2X7R selective antagonists, AZ10606120 and brilliant blue-G. In confocal micrographs from isolated terminals of the NH showed that P2X7R-immunoreactivity was localized in the plasma membranes. Lastly, the role of P2X7R on AVP release was tested. Our results showed that BzATP evoked sustained AVP release in NH terminals, which was inhibited by AZ10606120. Taken together, our data lead us to conclude that the P2X7R is expressed in NH terminals and corroborates its role in AVP secretion.