Paracellular transport of phosphate along the intestine

Inorganic phosphate (Pi) is crucial for many biological functions, such as energy metabolism, signal transduction, and pH buffering. Efficient systems must exist to ensure sufficient supply for the body of Pifrom diet. Previous experiments in humans and rodents suggest that two pathways for the absorption of Piexist, an active transcellular Pitransport and a second paracellular pathway. Whereas the identity, role, and regulation of active Pitransport have been extensively studied, much less is known about the properties of the paracellular pathway. In Ussing chamber experiments, we characterized paracellular intestinal Pipermeabilities and fluxes. Dilution potential measurements in intestinal cell culture models demonstrated that the tight junction is permeable to Pi, with monovalent Pihaving a higher permeability than divalent Pi. These findings were confirmed in rat and mouse intestinal segments by use of Ussing chambers and a combination of dilution potential measurements and fluxes of radiolabeled32Pi. Both techniques yielded very similar results, showing that paracellular Pifluxes were bidirectional and that Pipermeability was ~50% of the permeability for Na+or Cl−. Pifluxes were a function of the concentration gradient and Pispecies (mono- vs. divalent Pi). In mice lacking the active transcellular Pitransport component sodium-dependent Pitransporter NaPi-IIb, the paracellular pathway was not upregulated. In summary, the small and large intestines have a very high paracellular Pipermeability, which may favor monovalent Pifluxes and allow efficient uptake of Pieven in the absence of active transcellular Piuptake. NEW & NOTEWORTHY The paracellular permeability for phosphate is high along the entire axis of the small and large intestine. There is a slight preference for monovalent phosphate. Paracellular phosphate fluxes do not increase when transcellular phosphate transport is genetically abolished. Paracellular phosphate transport may be an important target for therapies aiming to reduce intestinal phosphate absorption.