Evidence for a signaling axis by which intestinal phosphate rapidly modulates renal phosphate reabsorption

被引:120
作者
Berndt, Theresa
Thomas, Leslie F.
Craig, Theodore A.
Sommer, Stacy
Li, Xujian
Bergstralh, Eric J.
Kumar, Rajiv
机构
[1] Mayo Clin, Div Nephrol & Hypertens, Dept Internal Med, Rochester, MN 55905 USA
[2] Mayo Clin, Div Biostat, Dept Hlth Sci Res, Rochester, MN 55905 USA
[3] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA
关键词
1,25-dihydroxyvitamin D; FGF-23; fractional excretion of phosphate; intestinal phosphate absorption; secreted frizzled related protein-4;
D O I
10.1073/pnas.0704446104
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mechanisms by which phosphorus homeostasis is preserved in mammals are not completely understood. We demonstrate the presence of a mechanism by which the intestine detects the presence of increased dietary phosphate and rapidly increases renal phosphate excretion. The mechanism is of physiological relevance because it maintains plasma phosphate concentrations in the normal range after ingestion of a phosphate-containing meal. When inorganic phosphate is infused into the duodenum, there is a rapid increase in the renal fractional excretion of phosphate (FE Pi). The phosphaturic effect of intestinal phosphate is specific for phosphate because administration of sodium chloride does not elicit a similar response. Phosphaturia after intestinal phosphate administration occurs in thyro-parathyroidectomized rats, demonstrating that parathyroid hormone is not essential for this effect. The increase in renal FE Pi in response to the intestinal administration of phosphate occurs without changes in plasma concentrations of phosphate (filtered load), parathyroid hormone, FGF-23, or secreted frizzled related protein-4. Denervation of the kidney does not attenuate phosphaturia elicited after intestinal phosphate administration. Phosphaturia is not elicited when phosphate is instilled in other parts of the gastrointestinal tract such as the stomach. Infusion of homogenates of the duodenal mucosa increases FE Pi, which demonstrates the presence of one or more substances within the intestinal mucosa that directly modulate renal phosphate reabsorption. Our experiments demonstrate the presence of a previously unrecognized phosphate gut-renal axis that rapidly modulates renal phosphate excretion after the intestinal administration of phosphate.
引用
收藏
页码:11085 / 11090
页数:6
相关论文
共 74 条
[1]  
Aurbach G D, 1972, Recent Prog Horm Res, V28, P353
[2]   PARATHYROID-HORMONE AND CALCITONIN REGULATION OF RENAL-FUNCTION [J].
AURBACH, GD ;
HEATH, DA .
KIDNEY INTERNATIONAL, 1974, 6 (05) :331-345
[3]   The gut and energy balance: Visceral allies in the obesity wars [J].
Badman, MK ;
Flier, JS .
SCIENCE, 2005, 307 (5717) :1909-1914
[4]   EFFECTS OF ACUTE UNILATERAL RENAL DENERVATION IN RAT [J].
BELLOREUSS, E ;
COLINDRES, RE ;
PASTORIZAMUNOZ, E ;
MUELLER, RA ;
GOTTSCHALK, CW .
JOURNAL OF CLINICAL INVESTIGATION, 1975, 56 (01) :208-217
[5]   Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent [J].
Berndt, T ;
Craig, TA ;
Bowe, AE ;
Vassiliadis, J ;
Reczek, D ;
Finnegan, R ;
De Beur, SMJ ;
Schiavi, SC ;
Kumar, R .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 112 (05) :785-794
[6]  
Berndt T., 1992, KIDNEY PHYSL PATHOPH, P2511
[7]   Phosphatonins and the regulation of phosphate homeostasis [J].
Berndt, Theresa ;
Kumar, Rajiv .
ANNUAL REVIEW OF PHYSIOLOGY, 2007, 69 :341-359
[8]   Phosphatonins and the regulation of phosphorus homeostasis [J].
Berndt, TJ ;
Schiavi, S ;
Kumar, R .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2005, 289 (06) :F1170-F1182
[9]   The ATP synthase - A splendid molecular machine [J].
Boyer, PD .
ANNUAL REVIEW OF BIOCHEMISTRY, 1997, 66 :717-749
[10]  
Buchan AMJ, 1999, AM J PHYSIOL-GASTR L, V277, pG1103, DOI 10.1152/ajpgi.1999.277.6.G1103