Wang Tong
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Curr Opin Nephrol Hypertens. 2006 Sep;15(5):530-6. doi: 10.1097/01.mnh.0000242180.46362.c4.
It is well recognized that an increase in glomerular filtration rate leads to an increase in fluid, Na+ and HCO3- absorption in proximal tubules; however, underlying mechanisms of this modulation have not been delineated. This review provides an update of flow-activated transport events along the nephron. Transporters, flow-sensors and secondary messengers that may modulate flow are also discussed.
We have demonstrated that both NHE3 and H-ATPase activities are modulated by axial flow in mouse proximal tubules in vitro. Experimental data and modeling calculations provide strong evidence that brush-border microvilli function as flow sensors in the proximal tubule. In addition, AngII receptor localization is regulated by flow in cultured proximal tubule cells, and flow induces eNOS translocation in TAL.
Flow-modulated NHE3 activity is the regulatory mechanism for GTB. It is independent of neuron and systemic hormonal regulation, but requires the intact actin cytoskeleton to transmit the signal of altered axial flow sensed by brush-border microvilli. Unanswered questions include the identification of specific signaling transduction mechanisms and second messengers in response to flow. Whether the Na+/2Cl-/K+-cotransporter in TAL is flow-activated, and whether a divalent cation, Ca2+ and Mg2+ transport, can be regulated by flow is unknown.
肾小球滤过率增加会导致近端小管对液体、Na⁺和HCO₃⁻的重吸收增加，这一点已得到广泛认可；然而，这种调节的潜在机制尚未明确。本综述对沿肾单位的流量激活转运事件进行了更新。还讨论了可能调节流量的转运体、流量传感器和第二信使。
我们已经证明，在体外小鼠近端小管中，NHE3和H⁺-ATP酶的活性均受轴向流量调节。实验数据和模型计算提供了有力证据，表明刷状缘微绒毛在近端小管中充当流量传感器。此外，在培养的近端小管细胞中，血管紧张素II受体的定位受流量调节，且流量可诱导髓袢升支粗段中内皮型一氧化氮合酶易位。
流量调节的NHE3活性是肾小球滤过率调节的机制。它独立于神经和全身激素调节，但需要完整的肌动蛋白细胞骨架来传递由刷状缘微绒毛感知的轴向流量改变的信号。尚未解决的问题包括确定响应流量的特定信号转导机制和第二信使。髓袢升支粗段中的Na⁺/2Cl⁻/K⁺共转运体是否受流量激活，以及二价阳离子Ca²⁺和Mg²⁺的转运是否可受流量调节尚不清楚。
