NDLI: Regulation of glomerulotubular balance: flow-activated proximal tubule function

Content Provider	Springer Nature Link
Author	Wang, Tong Weinbaum, Sheldon Weinstein, Alan M.
Copyright Year	2017
Abstract	The purpose of this review is to summarize our knowledge and understanding of the physiological importance and the mechanisms underlying flow-activated proximal tubule transport. Since the earliest micropuncture studies of mammalian proximal tubule, it has been recognized that tubular flow is an important regulator of sodium, potassium, and acid-base transport in the kidney. Increased fluid flow stimulates Na+ and HCO3 − absorption in the proximal tubule via stimulation of Na/H-exchanger isoform 3 (NHE3) and H+-ATPase. In the proximal tubule, brush border microvilli are the major flow sensors, which experience changes in hydrodynamic drag and bending moment as luminal flow velocity changes and which transmit the force of altered flow to cytoskeletal structures within the cell. The signal to NHE3 depends upon the integrity of the actin cytoskeleton; the signal to the H+-ATPase depends upon microtubules. We have demonstrated that alterations in fluid drag impact tubule function by modulating ion transporter availability within the brush border membrane of the proximal tubule. Beyond that, there is evidence that transporter activity within the peritubular membrane is also modulated by luminal flow. Secondary messengers that regulate the flow-mediated tubule function have also been delineated. Dopamine blunts the responsiveness of proximal tubule transporters to changes in luminal flow velocity, while a DA1 antagonist increases flow sensitivity of solute reabsorption. IP3 receptor-mediated intracellular Ca2+ signaling is critical to transduction of microvillus drag. In this review, we summarize our findings of the regulatory mechanism of flow-mediated Na+ and HCO3 − transport in the proximal tubule and review available information about flow sensing and regulatory mechanism of glomerulotubular balance.
Starting Page	643
Ending Page	654
Page Count	12
File Format	PDF
ISSN	00316768
Journal	Pflügers Archiv
Volume Number	469
Issue Number	5-6
e-ISSN	14322013
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2017-03-07
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Flow dependent Kidney NaCl HCO3 − Transport Flow sensors Calcium signals Human Physiology Molecular Medicine Neurosciences Cell Biology Receptors
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical) Clinical Biochemistry

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