Regulation of rat intestinal Na-dependent phosphate transporters by dietary phosphate.
Hyperphosphatemia associated with chronic kidney disease is one of the factors that can promote vascular calcification, and intestinal P(i) absorption is one of the pharmacological targets that prevents it. The type II Na-P(i) cotransporter NaPi-2b is the major transporter that mediates P(i) reabsorption in the intestine. The potential role and regulation of other Na-P(i) transporters remain unknown. We have identified expression of the type III Na-P(i) cotransporter PiT-1 in the apical membrane of enterocytes. Na-P(i) transport activity and NaPi-2b and PiT-1 proteins are mostly expressed in the duodenum and jejunum of rat small intestine; their expression is negligible in the ileum. In response to a chronic low-P(i) diet, there is an adaptive response restricted to the jejunum, with increased brush border membrane (BBM) Na-P(i) transport activity and NaPi-2b, but not PiT-1, protein and mRNA abundance. However, in rats acutely switched from a low- to a high-P(i) diet, there is an increase in BBM Na-P(i) transport activity in the duodenum that is associated with an increase in BBM NaPi-2b protein abundance. Acute adaptive upregulation is restricted to the duodenum and induces an increase in serum P(i) that produces a transient postprandial hyperphosphatemia. Our study, therefore, indicates that Na-P(i) transport activity and NaPi-2b protein expression are differentially regulated in the duodenum vs. the jejunum and that postprandial upregulation of NaPi-2b could be a potential target for treatment of hyperphosphatemia.
Giral
Hector
H
Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Denver, and Veterans Affairs Medical Center, Aurora, CO 80045, USA. Hector.Giral-Arnal@ucdenver.edu
Caldas
Yupanqui
Y
Sutherland
Eileen
E
Wilson
Paul
P
Breusegem
Sophia
S
Barry
Nicholas
N
Blaine
Judith
J
Jiang
Tao
T
Wang
Xiaoxin X
XX
Levi
Moshe
M
D000818:Animals; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism*; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D010710:Phosphates / Q000494:pharmacology*; D016226:Phosphorus, Dietary / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D050608:Sodium-Phosphate Cotransporter Proteins / Q000096:biosynthesis*; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000096:biosynthesis / Q000235:genetics; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb / Q000096:biosynthesis
D010710:Phosphates; D016226:Phosphorus, Dietary; D012333:RNA, Messenger; C493588:Slc20a1 protein, rat; C493559:Slc34a2 protein, rat; D050608:Sodium-Phosphate Cotransporter Proteins; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb
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