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 of the body with Pi from diet. Previous experiments in humans and rodents suggest that two pathways for the absorption of Pi exist, an active transcellular Pi transport and a second paracellular pathway. Whereas the identity, role and regulation of active Pi transport has been extensively studied, much less is known about the properties of the paracellular pathway. In Ussing chamber experiments we characterized paracellular intestinal Pi permeabilities and fluxes. Dilution potential measurements in intestinal cell culture models demonstrated that the tight junction is permeable to Pi , with monovalent Pi having a higher permeability than divalent Pi . These findings were confirmed in rat and mouse intestinal segments using Ussing chambers and a combination of dilution potential measurements and fluxes of radiolabeled 32 Pi . Both techniques yielded very similar results showing that paracellular Pi fluxes were bidirectional and that Pi permeability was about 50% of the permeability for Na+ or Cl- . Pi fluxes were a function of the concentration gradientand Pi species (mono- vs. divalent Pi ). In mice lacking the active transcellular Pi transport component, NaPi-IIb, the paracellular pathway was not upregulated. In summary, the small and large intestine have a very high paracellular Pi permeability that may favor monovalent Pi fluxes and allows efficient uptake of Pi even in the absence of active transcellular Pi uptake.