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Transcellular And Paracellular Permeability For Phosphate Along The Intestinal Epithelia
Author(s) -
Hernando Nati,
Knöpfel Thomas,
Himmerkus Nina,
Günzel Dorothee,
Bleich Markus,
Wagner Carsten A.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.747.22
Subject(s) - paracellular transport , transcellular , ussing chamber , ileum , intestinal permeability , intestinal epithelium , jejunum , reabsorption , medicine , cotransporter , chemistry , homeostasis , endocrinology , biology , kidney , epithelium , biochemistry , permeability (electromagnetism) , pathology , secretion , sodium , membrane , organic chemistry
Background Homeostasis of inorganic phosphate (Pi) is mostly achieved by regulating its intestinal and renal (re)absorption. Because hyperphosphatemia associates with cardiovascular disease in the general population as well as with poor prognosis in patients with chronic kidney disease, intestinal absorption of dietary Pi has been considered as a possible therapeutic target. Transcellular transport of Pi across intestinal and renal epithelia is mediated by Na + /Pi transporters from the Slc20 and Slc34 families of solute carriers. Intestinal expression of Slc34a2/NaPi‐IIb is restricted to the luminal membrane of enterocytes. In mice, the cotransporter is mostly localized in the ileum, whereas duodenum and jejunum are the segments with higher expression in humans and rats. Intestinal‐specific ablation of Slc34a2 in mice abrogates the active transport of Pi in the ileum but only triggers mild fecal Pi loss, which under normal dietary conditions is compensated by increased renal reabsorption. Moreover, loading of dietary Pi leads to hyperphosphaturia even in the absence of NaPi‐IIb, suggesting alternative pathways for intestinal absorption of Pi. In this regard, early studies already proposed the presence of a passive paracellular component for Pi‐transport in the gut epithelia. Objective of the study The aim of this work was to analyze the capacity of the intestinal tract of rats and mice to absorb Pi paracellularly, and to study the effect of Slc34a2 ablation on the paracellular permeability. For that purpose, intestinal segments where mounted in Ussing chambers and paracellular transport was studied by electrophysiological and 32 P‐flux means. Results We found that: a) Intestinal tight junctions of rats and mice are indeed permeable to Pi, as indicated by the linear relationship between Pi‐induced currents and 32 P‐fluxes with the transepithelial Pi‐gradient, as well as by the bi‐directionality of transport. b) Intestinal tight junctions seem to discriminate between monovalent (PO 4 H 2 − ) and divalent (PO 4 H 2 − ) Pi, been more permeable to the monovalent ion. This is in contrast to NaPi‐IIb, which preferent substrate is the divalent ion. The paracellular permeability for PO 4 H 2 − was found to be relatively large, about half of that for Na + . c) In rats, the small intestine shows higher permeability for Pi than the colon, whereas small and large intestine display similar permeabilities in mice. d) Depletion of Slc34a2 does not change the paracellular transport of Pi in mice. Conclusions Together, our data suggests that the tight junctions of the intestinal epithelia are largely permeable to Pi, and that this permeability is not affected by the absence of Slc34a2 /NaPi‐IIb. The presence of a large passive component should probably be considered to achieve an efficient inhibition of intestinal absorption of Pi. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .