Systemic network for dietary inorganic phosphate adaptation among three organs
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Inorganic phosphate (Pi) secretion from the salivary glands and dietary Pi are key Pi sources. The regulatory mechanisms of Pi homeostasis in the salivary glands are unknown. We investigated how salivary Pi concentrations are regulated by dietary Pi in mouse models. Dietary manipulation significantly changed the levels of Npt2b protein in the salivary gland ductal cells. In addition, rapid feeding on a high-Pi diet increased the saliva Pi concentrations and led to rapid endocytosis of Npt2b in the apical membranes of the duct cells. Global Npt2b± mice exhibited increased salivary Pi concentrations and intestine-specific deletion of Npt2b after high Pi loading increased the salivary Pi concentrations. These findings indicate that Npt2b levels in the salivary glands affect the salivary Pi concentration and are regulated by dietary Pi. Intestinal Npt2b levels might also affect salivary Pi concentrations as well as renal Pi excretion. These findings suggest Pi is endogenously recycled by salivary Pi secretion, intestinal Pi absorption, and renal Pi excretion.
KeywordsPhosphate Kidney Intestine Salivary glands Transporter
We thank the Daiichi-Sankyo Pharmaceutical Co. (Tokyo, Japan) for providing the cevimeline. K.I., H.S., and K-I.M. conceived of and designed the research; K.I., H.S., A.H., T. F., I. K., S.T., and Y.I. performed the experiments; K.I., H.S., and K-I.M. analyzed the data; K.I., and H.S. prepared the figures; K.I., H.S., and K-I.M. drafted the manuscript. The technical assistance of Tomo Mukai, Shohei Sasaki, Ayaka Mori, and Shihoko Yuki is gratefully acknowledged.
This work was supported by the Ministry of Education, Culture, Sports, Science, and Technology of Japan (No. 23689045 to H. Segawa, No. 26293204 to K. Miyamoto), and The Salt Science Research Foundation (Japan).
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Conflict of interest
The authors declare that they have no conflict of interest.
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