Intestinal phosphate absorption is mediated by multiple transport systems in rats.

Apical inorganic phosphate (P) transport in the small intestine seems to be mainly mediated by the sodium/P cotransporter NaPi2b. To verify this role, we have studied the combined effects of pH, phosphonoformate, and P deprivation on intestinal P transport. Rats were fed, ad libitum, three fodders containing 1.2, 0.6, or 0.1% P for 1, 5, or 10 days. P deprivation (0.1%) increased both sodium-activated and sodium-independent P transport in brush-border membrane vesicles from the duodenum and jejunum for all three times. Alkaline pH inhibited P transport, despite the increasing concentration of [Formula: see text] (NaPi2b substrate), whereas acidity increased transport when the concentration of the PiT1/PiT2 substrate, [Formula: see text], was at its highest. The effect of P deprivation was maximal at acid pH, but both basal and upregulated transport were inhibited (70%) with phosphonoformate, an inhibitor of NaPi2b. PiT2 and NaPi2b protein abundance increased after 24 h of P deprivation in the duodenum, jejunum, and ileum, whereas PiT1 required 5-10 days in the duodenum and jejunum. Therefore, whereas transporter expressions are partially correlated with P transport adaptation, the pH effect precludes NaPi2b, and phosphonoformic acid precludes PiT1 and PiT2 as the main transporters. Transport and transporter expression were also inconsistent when feeding was limited to 4 h daily, because the 1.2% P diet paradoxically increased P transport in the duodenum and jejunum, but NaPi2b and PiT1 expressions only increased with the 0.1% diet. These findings suggest the presence of a major transporter that carries [Formula: see text] and is inhibited by phosphonoformate. The combined effects of dietary inorganic phosphate (P) content, pH, and phosphonoformate inhibition suggest that the resulting apical P transport in the small intestine cannot be fully explained by the presence of NaPi2b, PiT1, or PiT2. We provide evidence of the presence of a new sodium-coupled P transporter that uses [Formula: see text] as the preferred substrate and is inhibited by phosphonoformate, and its expression correlates with P transport in all assayed conditions.