title: Intestinal phosphate absorption is mediated by multiple transport systems in rats.
abstract: Apical inorganic phosphate (Pi) transport in the small intestine seems to be mainly mediated by the sodium/Picotransporter NaPi2b. To verify this role, we have studied the combined effects of pH, phosphonoformate, and Pideprivation on intestinal Pitransport. Rats were fed, ad libitum, three fodders containing 1.2, 0.6, or 0.1% Pifor 1, 5, or 10 days. Pideprivation (0.1%) increased both sodium-activated and sodium-independent Pitransport in brush-border membrane vesicles from the duodenum and jejunum for all three times. Alkaline pH inhibited Pitransport, 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 Pideprivation 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 Pideprivation 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 Pitransport 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% Pidiet paradoxically increased Pitransport 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 & NOTEWORTHYThe combined effects of dietary inorganic phosphate (Pi) content, pH, and phosphonoformate inhibition suggest that the resulting apical Pitransport 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 Pitransporter that uses [Formula: see text] as the preferred substrate and is inhibited by phosphonoformate, and its expression correlates with Pitransport in all assayed conditions.
authors.affiliation: Department of Toxicology, University of Zaragoza, Zaragoza, Spain; and.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Candeal
authors.affiliation: Department of Toxicology, University of Zaragoza, Zaragoza, Spain; and.|Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Denver, Aurora, Colorado.
authors.forename: Yupanqui A
authors.initials: YA
authors.lastname: Caldas
authors.affiliation: Department of Toxicology, University of Zaragoza, Zaragoza, Spain; and.
authors.forename: Natalia
authors.initials: N
authors.lastname: Guillén
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Denver, Aurora, Colorado.
authors.forename: Moshe
authors.initials: M
authors.lastname: Levi
authors.affiliation: Department of Toxicology, University of Zaragoza, Zaragoza, Spain; and sorribas@unizar.es.
authors.forename: Víctor
authors.identifier: http://orcid.org/0000-0003-3457-323X
authors.initials: V
authors.lastname: Sorribas
mesh_terms: D000818:Animals; D001692:Biological Transport; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism*; D010710:Phosphates / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb / Q000235:genetics / Q000378:metabolism
chemical_list: D010710:Phosphates; C493559:Slc34a2 protein, rat; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb
keywords: NaPi2b; Pi deprivation; Pi transport; PiT1; PiT2; pH dependence; small intestine