Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, Japan.
J Neurosci Res. 2010 Jul;88(9):1995-2006. doi: 10.1002/jnr.22370.
Systemic osmotic homeostasis is regulated mainly by neuroendocrine system of arginine-vasopressin (AVP) in mammalians. In the present study, we demonstrated that the immunoreactivity of tissue plasminogen activator (tPA) was observed specifically at neurosecretory granules of AVP-positive magnocellular terminals and that of plasminogen was seen at astrocytes in the neurohypophysis (NH). Both tPA and plasminogen knockout (KO) mice revealed higher plasma osmolarity upon water deprivation, a chronic osmotic stimulation, as compared with their wild-type (WT) animals, indicating abnormal osmotic control in these KO mice. tPA KO mice but not plasminogen ones revealed lower ability in secreting AVP into the blood circulation upon an acute osmotic stimulation. Both tPA and plasminogen KO animals showed lower ability in secreting AVP into the blood circulation upon a chronic osmotic stimulation. The recombinant tPA was able to promote the release of AVP from isolated NH. Chronic osmotic stimulation decreased the laminin expression level of neurohypophysial microvessel in WT mice but not in plasminogen KO ones. We suggest that AVP secretion is critically regulated by tPA-dependent facilitation of AVP release from terminals and plasminogen-dependent increase of AVP permeability across microvessels possibly via laminin degradation.
哺乳动物的全身渗透稳态主要由精氨酸加压素（AVP）的神经内分泌系统调节。在本研究中，我们证明了组织型纤溶酶原激活物（tPA）的免疫反应性特异性地观察到 AVP 阳性大细胞末端的神经分泌颗粒中，而纤溶酶原则在神经垂体（NH）的星形胶质细胞中观察到。与野生型（WT）动物相比，tPA 和纤溶酶原敲除（KO）小鼠在禁水和慢性渗透刺激后表现出更高的血浆渗透压，表明这些 KO 小鼠的渗透控制异常。tPA KO 小鼠而非纤溶酶原 KO 小鼠在急性渗透刺激下向血液循环中分泌 AVP 的能力较低。tPA 和纤溶酶原 KO 动物在慢性渗透刺激下向血液循环中分泌 AVP 的能力均较低。重组 tPA 能够促进从分离的 NH 释放 AVP。慢性渗透刺激降低了 WT 小鼠神经垂体微血管的层粘连蛋白表达水平，但在纤溶酶原 KO 小鼠中则没有。我们认为，AVP 的分泌受到 tPA 依赖性促进 AVP 从末端释放和纤溶酶原依赖性增加 AVP 穿过微血管的通透性的严格调节，可能通过层粘连蛋白降解。
