Systemic network for dietary inorganic phosphate adaptation among three organs
- 169 Downloads
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).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 10.Homann V, Rosin-Steiner S, Stratmann T, Arnold WH, Gaengler P, Kinne RK (2005) Sodium-phosphate cotransporter in human salivary glands: molecular evidence for the involvement of NPT2b in acinar phosphate secretion and ductal phosphate reabsorption. Arch Oral Biol 50:759–768. https://doi.org/10.1016/j.archoralbio.2005.01.009 CrossRefGoogle Scholar
- 16.Marks J, Lee GJ, Nadaraja SP, Debnam ES, Unwin RJ (2015) Experimental and regional variations in Na+-dependent and Na+-independent phosphate transport along the rat small intestine and colon. Phys Rep 3. https://doi.org/10.14814/phy2.12281
- 20.Ohi A, Hanabusa E, Ueda O, Segawa H, Horiba N, Kaneko I, Kuwahara S, Mukai T, Sasaki S, Tominaga R, Furutani J, Aranami F, Ohtomo S, Oikawa Y, Kawase Y, Wada NA, Tachibe T, Kakefuda M, Tateishi H, Matsumoto K, Tatsumi S, Kido S, Fukushima N, Jishage K, Miyamoto K (2011) Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b(+)/(−) mice. Am J Physiol Ren Physiol 301:F1105–F1113. https://doi.org/10.1152/ajprenal.00663.2010 CrossRefGoogle Scholar
- 21.Pan Y, Iwata F, Wang D, Muraguchi M, Ooga K, Ohmoto Y, Takai M, Cho G, Kang J, Shono M, Li XJ, Okamura K, Mori T, Ishikawa Y (2009) Identification of aquaporin-5 and lipid rafts in human resting saliva and their release into cevimeline-stimulated saliva. Biochim Biophys Acta 1790:49–56. https://doi.org/10.1016/j.bbagen.2008.08.009 CrossRefGoogle Scholar
- 23.Romanenko VG, Nakamoto T, Catalan MA, Gonzalez-Begne M, Schwartz GJ, Jaramillo Y, Sepulveda FV, Figueroa CD, Melvin JE (2008) Clcn2 encodes the hyperpolarization-activated chloride channel in the ducts of mouse salivary glands. Am J Physiol Gastrointest Liver Physiol 295:G1058–G1067. https://doi.org/10.1152/ajpgi.90384.2008 CrossRefGoogle Scholar
- 30.Wagner CA, Rubio-Aliaga I, Hernando N (2017) Renal phosphate handling and inherited disorders of phosphate reabsorption: an update. Pediatr Nephrol. https://doi.org/10.1007/s00467-017-3873-3