NaPi-mediated transcellular permeation is the dominant route in intestinal inorganic phosphate absorption in rats.
Inorganic phosphate in food is absorbed two ways, the transcellular route via the brush border membrane and the paracellular route via tight junctions. NaPi, a sodium-dependent inorganic phosphate transporter, is expressed in rat and human intestine. However, the relative contribution of NaPi to total carrier-mediated transport of physiological concentrations of inorganic phosphate in rat intestine is not clear. Here, we characterized inorganic phosphate transport across the rat small intestine using a voltage-clamp analysis which allowed the diffrentiation of inorganic phosphate permeation through these two (transcellular and paracellular) routes. Results showed that, under a physiologically normal transmucosal electrical potential difference (about 2 mV), permeation of inorganic phosphate by the transcellular route was greater than that by the paracellular route. Further, transport was significantly decreased by the addition to the incubation medium of phosphonoformic acid, a sodium-dependent phosphate transporter inhibitor, and severely inhibited under sodium-free conditions. Similar results were obtained without the voltage-clamp. Together, these results suggest that NaPi-mediated transcellular permeation is the dominant route in the absorption of inorganic phosphate across the small intestine.
Eto
Nobuaki
N
Pharmaceutical Research Laboratories, Kirin Brewery Co., Ltd., Gunma, 370-1295, Japan.
Tomita
Mikio
M
Hayashi
Masahiro
M
D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D017245:Foscarnet / Q000494:pharmacology; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010710:Phosphates / Q000378:metabolism / Q000493:pharmacokinetics*; D010761:Phosphorus Radioisotopes; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000494:pharmacology; D050608:Sodium-Phosphate Cotransporter Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*
D010710:Phosphates; D010761:Phosphorus Radioisotopes; D050608:Sodium-Phosphate Cotransporter Proteins; D017245:Foscarnet; D012965:Sodium Chloride; D011189:Potassium Chloride