Substrates and inhibitors of phosphate transporters: from experimental tools to pathophysiological relevance

  • Víctor SorribasEmail author
  • Natalia Guillén
  • Cecilia Sosa
Invited Review


The control of inorganic phosphate homeostasis is mediated through the activity of sodium-coupled Pi transporters located in the intestine, kidneys, and bone. To study these transporters in either the native tissue or after heterologous expression, it is very important to use specific inhibitors of the studied transporter, in order to know the corresponding relevance in the total Pi uptake and to differentiate from the activity of other transporters. Inhibitors are also necessary as drugs for treating Pi homeostasis disorders. Under normal physiological conditions, the renal and intestinal excretion of Pi matches dietary intestinal absorption, but when the number of non-functional nephrons increase in chronic kidney disease and end-stage renal disease, the excretion of surplus Pi is progressively impaired, thereby increasing the risk of hyperphosphatemia and Pi toxicity. When the compensatory mechanisms that increase Pi excretion fail, Pi toxicity can only be prevented by reducing the intestinal absorption of Pi through phosphate binders that reduced the free Pi concentration in the lumen, and inhibitors of intestinal Pi transporters and of the paracellular absorption route. Although many potentially interesting inhibitors have been reported to date, only a few are available for experimental purposes, and even fewer have been used in independent clinical trials. In this review, we summarize the different groups of compounds reported to date as inhibitors of Pi transport. To help understand and characterize the inhibition mechanisms, we also summarize the kinetic analysis approaches and screening methods that could be applied.


Pi transport Inhibitors NaPi-IIa NaPi-IIb NaPi-IIc Pi homeostasis 


Funding information

This work has been supported by grant SAF2015-66705-P from the Spanish Ministry of Economy and Competitiveness to all the authors.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Authors and Affiliations

  1. 1.Department of Toxicology, Veterinary FacultyUniversity of ZaragozaZaragozaSpain

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