Department of Microbiology and Physiological Systems & Program in Neuroscience, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Cell Calcium. 2012 Mar-Apr;51(3-4):284-92. doi: 10.1016/j.ceca.2012.01.008. Epub 2012 Feb 17.
The hypothalamic-neurohypophysial system (HNS) controls diuresis and parturition through the release of arginine-vasopressin (AVP) and oxytocin (OT). These neuropeptides are chiefly synthesized in hypothalamic magnocellular somata in the supraoptic and paraventricular nuclei and are released into the blood stream from terminals in the neurohypophysis. These HNS neurons develop specific electrical activity (bursts) in response to various physiological stimuli. The release of AVP and OT at the level of neurohypophysis is directly linked not only to their different burst patterns, but is also regulated by the activity of a number of voltage-dependent channels present in the HNS nerve terminals and by feedback modulators. We found that there is a different complement of voltage-gated Ca(2+) channels (VGCC) in the two types of HNS terminals: L, N, and Q in vasopressinergic terminals vs. L, N, and R in oxytocinergic terminals. These channels, however, do not have sufficiently distinct properties to explain the differences in release efficacy of the specific burst patterns. However, feedback by both opioids and ATP specifically modulate different types of VGCC and hence the amount of AVP and/or OT being released. Opioid receptors have been identified in both AVP and OT terminals. In OT terminals, μ-receptor agonists inhibit all VGCC (particularly R-type), whereas, they induce a limited block of L-, and P/Q-type channels, coupled to an unusual potentiation of the N-type Ca(2+) current in the AVP terminals. In contrast, the N-type Ca(2+) current can be inhibited by adenosine via A(1) receptors leading to the decreased release of both AVP and OT. Furthermore, ATP evokes an inactivating Ca(2+)/Na(+)-current in HNS terminals able to potentiate AVP release through the activation of P2X2, P2X3, P2X4 and P2X7 receptors. In OT terminals, however, only the latter receptor type is probably present. We conclude by proposing a model that can explain how purinergic and/or opioid feedback modulation during bursts can mediate differences in the control of neurohypophysial AVP vs. OT release.
下丘脑-神经垂体系统（HNS）通过释放精氨酸血管加压素（AVP）和催产素（OT）来控制利尿和分娩。这些神经肽主要在视上核和室旁核的下丘脑大细胞体中合成，并从神经垂体中的末端释放到血液中。这些 HNS 神经元对各种生理刺激产生特定的电活动（爆发）。神经垂体中 AVP 和 OT 的释放不仅与它们不同的爆发模式直接相关，还受到 HNS 神经末梢中存在的许多电压依赖性通道的活动和反馈调节剂的调节。我们发现，两种类型的 HNS 末梢中存在不同的电压门控 Ca(2+)通道（VGCC）组成：血管加压素能末梢中的 L、N 和 Q 与催产素能末梢中的 L、N 和 R。然而，这些通道的特性没有足够的差异来解释特定爆发模式释放效率的差异。然而，阿片类物质和 ATP 的反馈都特异性地调节不同类型的 VGCC，从而调节 AVP 和/或 OT 的释放量。阿片受体已在 AVP 和 OT 末梢中被鉴定。在 OT 末梢中，μ 受体激动剂抑制所有 VGCC（特别是 R 型），而它们诱导 L-和 P/Q-型通道的有限阻断，与 AVP 末梢中 N-型 Ca(2+)电流的异常增强相关。相反，N-型 Ca(2+)电流可被腺苷通过 A(1)受体抑制，导致 AVP 和 OT 的释放减少。此外，ATP 在 HNS 末梢中引发失活的 Ca(2+)/Na(+)电流，能够通过激活 P2X2、P2X3、P2X4 和 P2X7 受体增强 AVP 的释放。然而，在 OT 末梢中，可能只存在后一种受体类型。我们通过提出一个模型来得出结论，该模型可以解释在爆发期间嘌呤能和/或阿片类物质的反馈调节如何介导神经垂体 AVP 与 OT 释放控制的差异。
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