Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
J Cell Physiol. 2014 Oct;229(10):1336-45. doi: 10.1002/jcp.24563.
The microvascular network of the microcirculation works in tight communication with surrounding tissues to control blood supply and exchange of solutes. In cerebral circulation, microvascular endothelial cells constitute a selective permeability barrier that controls the environment of parenchymal brain tissue, which is known as the blood-brain barrier (BBB). Connexin- and pannexin-formed channels (gap junctions and hemichannels) play a central role in the coordination of endothelial and smooth muscle cell function and connexin-mediated signaling in endothelial cells is essential in the regulation of BBB permeability. Likewise, gap junction communication between astrocyte end-feet also contributes to maintain the BBB integrity, but the participation of hemichannels in this process cannot be discarded. Sympathetic and sensory perivascular nerves are also involved in the control and coordination of vascular function through the release of vasoconstrictor or vasodilator signals and by the regulation of gap junction communication in the vessel wall. Conversely, ATP release through pannexin-1-formed channels mediates the α1-adrenergic signaling. Furthermore, here we show that capsaicin-induced CGRP release from mesenteric perivascular sensory nerves induces pannexin-1-formed channel opening, which in turn leads to reduction of pannexin-1 and endothelial nitric oxide synthase (eNOS) expression along the time. Interestingly, blockade of CGRP receptors with CGRP8-37 increased eNOS expression by ∼5-fold, suggesting that capsaicin-sensitive sensory nerves are involved in the control of key signaling proteins for vascular function. In this review, we discuss the importance of connexin-based channels in the control of BBB integrity and the functional interaction of vascular connexins and pannexins with the peripheral nervous system.
微循环的微血管网络与周围组织紧密沟通，以控制血液供应和溶质交换。在脑循环中，微血管内皮细胞构成了一个选择性通透性屏障，控制着实质脑组织的环境，这被称为血脑屏障 (BBB)。连接蛋白和连接蛋白形成的通道（缝隙连接和半通道）在协调内皮细胞和平滑肌细胞功能以及内皮细胞中连接蛋白介导的信号转导中发挥核心作用，连接蛋白介导的信号转导对于调节 BBB 通透性至关重要。同样，星形胶质细胞终足之间的缝隙连接通讯也有助于维持 BBB 的完整性，但不能排除半通道在此过程中的参与。交感神经和感觉性血管周围神经也通过释放血管收缩或舒张信号以及调节血管壁中的缝隙连接通讯来参与血管功能的控制和协调。相反，通过连接蛋白 1 形成的通道释放的 ATP 通过介导α1-肾上腺素能信号转导。此外，我们在这里表明，辣椒素诱导的肠系膜血管周围感觉神经释放 CGRP 会诱导连接蛋白 1 形成的通道开放，这反过来又导致连接蛋白 1 和内皮型一氧化氮合酶 (eNOS) 的表达随时间减少。有趣的是，用 CGRP8-37 阻断 CGRP 受体使 eNOS 表达增加了约 5 倍，这表明辣椒素敏感的感觉神经参与了对血管功能关键信号蛋白的控制。在这篇综述中，我们讨论了连接蛋白基通道在控制 BBB 完整性以及血管连接蛋白和连接蛋白与外周神经系统的功能相互作用中的重要性。
