Intestinal phosphate absorption is mediated by multiple transport systems in rats

Apical inorganic phosphate (P_i) transport in the small intestine seems to be mainly mediated by the sodium/P_i cotransporter NaPi2b. To verify this role, we have studied the combined effects of pH, phosphonoformate, and P_i deprivation on intestinal P_i transport. Rats were fed, ad libitum, three fodders containing 1.2, 0.6, or 0.1% P_i for 1, 5, or 10 days. P_i deprivation (0.1%) increased both sodium-activated and sodium-independent P_i transport in brush-border membrane vesicles from the duodenum and jejunum for all three times. Alkaline pH inhibited P_i 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_i 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_i 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_i 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_i diet paradoxically increased P_i 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.NEW & NOTEWORTHY The combined effects of dietary inorganic phosphate (P_i) content, pH, and phosphonoformate inhibition suggest that the resulting apical P_i 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_i transporter that uses [Formula: see text] as the preferred substrate and is inhibited by phosphonoformate, and its expression correlates with P_i transport in all assayed conditions.