Paracellular transport of phosphate along the intestine

Inorganic phosphate (P_i) 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 P_i from diet. Previous experiments in humans and rodents suggest that two pathways for the absorption of P_i exist, an active transcellular P_i transport and a second paracellular pathway. Whereas the identity, role, and regulation of active P_i transport have been extensively studied, much less is known about the properties of the paracellular pathway. In Ussing chamber experiments, we characterized paracellular intestinal P_i permeabilities and fluxes. Dilution potential measurements in intestinal cell culture models demonstrated that the tight junction is permeable to P_i, with monovalent P_i having a higher permeability than divalent P_i. 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 radiolabeled ³²P_i. Both techniques yielded very similar results, showing that paracellular P_i fluxes were bidirectional and that P_i permeability was ~50% of the permeability for Na⁺ or Cl^-. P_i fluxes were a function of the concentration gradient and P_i species (mono- vs. divalent P_i). In mice lacking the active transcellular P_i transport component sodium-dependent P_i transporter NaPi-IIb, the paracellular pathway was not upregulated. In summary, the small and large intestines have a very high paracellular P_i permeability, which may favor monovalent P_i fluxes and allow efficient uptake of P_i even in the absence of active transcellular P_i uptake.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.