Department of Physiology and Biophysics, Water and Salt Research Center, Aarhus University, Aarhus, Denmark.
Curr Opin Nephrol Hypertens. 2011 Sep;20(5):518-22. doi: 10.1097/MNH.0b013e3283487393.
Extracellular ATP is an essential local signaling molecule in all organ systems. In the kidney, purinergic signaling is involved in an array of functions and this review highlights those of relevance for renal tubular transport.
Purinergic receptors are expressed in all renal tubular segments and their stimulation generally leads to transport inhibition. Recent evidence has identified the tubular lumen as a restricted space for purinergic signaling. The concentrations of ATP in the luminal fluids are sufficiently high to inflict a tonic inhibition of renal tubular absorption via P2 receptors. The apical P2Y2 receptor plays a crucial role in this process. ATP is released continuously into the tubular lumen. The release is augmented in response to an increase of tubular flow and after stimulation of G-protein-coupled receptors. The primary cilium appears necessary for flow-stimulated luminal ATP release. Tubular ATP secretion may occur via nonjunctional connexin-hemichannels (connexin 30), which are strategically placed in the apical membrane of distal tubular intercalated cells and can be activated by tubular flow.
The tubular lumen has been discovered as an important signaling compartment in which local purinergic signaling determines an inhibitory tone for renal tubular transport. Blocking components of this system leads to tubular hyper-absorption, volume retention and elevated blood pressure.
细胞外 ATP 是所有器官系统中必不可少的局部信号分子。在肾脏中，嘌呤能信号参与了一系列功能，本综述重点介绍了与肾小管转运相关的功能。
嘌呤能受体在所有肾小管节段均有表达，其刺激通常会导致转运抑制。最近的证据表明，管状腔是嘌呤能信号的受限空间。管腔液中 ATP 的浓度足够高，可以通过 P2 受体对肾小管吸收产生持续的抑制作用。顶端 P2Y2 受体在这个过程中起着至关重要的作用。ATP 不断被释放到管状腔中。在管状流量增加和 G 蛋白偶联受体刺激后，释放会增加。初级纤毛似乎是流量刺激管腔 ATP 释放所必需的。管状 ATP 分泌可能通过非连接缝隙连接半通道（连接蛋白 30）发生，该通道位于远端肾小管闰盘细胞的顶端膜上，并可被管状流量激活。
管状腔已被发现为一个重要的信号室，其中局部嘌呤能信号决定了肾小管转运的抑制性基调。阻断该系统的成分会导致管状过度吸收、容量保留和血压升高。
