Evidence for a signaling axis by which intestinal phosphate rapidly modulates renal phosphate reabsorption
Evidence for a signaling axis by which intestinal phosphate rapidly modulates renal phosphate reabsorption
复制标题
DOI：
10.1073/pnas.0704446104
复制
发表时间：
2007-06-26
影响因子：
11.1
通讯作者：
Kumar, Rajiv
中科院分区：
文献类型：
--
作者：
Berndt, Theresa;Thomas, Leslie F.;Kumar, Rajiv
哺乳动物体内维持磷平衡的机制尚不完全清楚。我们证明了存在一种机制，通过这种机制，肠道可以检测到增加的膳食磷酸盐的存在，并迅速增加肾脏磷酸盐的排泄。这一机制具有生理相关性，因为它在摄入含磷膳食后将血浆磷浓度维持在正常范围内。当无机磷被注入十二指肠时，肾脏的磷酸盐排泄分数(FEPI)迅速增加。肠道磷酸盐的磷酸盐效应是磷酸盐所特有的，因为给药氯化钠不会引起类似的反应。去甲状旁腺的大鼠在肠道注射磷酸盐后出现磷尿症，说明甲状旁腺激素对这种作用不是必需的。肠道给予磷酸盐后，肾脏FEPI的增加不会改变血浆中磷酸盐(过滤负荷)、甲状旁腺激素、成纤维细胞生长因子-23或分泌的卷曲相关蛋白-4的浓度。去神经肾脏并不能减轻肠道磷酸盐给药后引起的磷尿症。当磷酸盐被注入胃等胃肠道的其他部位时，不会引发磷酸尿症。十二指肠粘膜匀浆的输注增加了FE PI，这表明肠粘膜内存在一种或多种物质，直接调节肾脏磷酸盐的重吸收。我们的实验证明，在肠道给药后，存在一个以前未被识别的磷酸盐肠-肾轴，该轴快速调节肾脏磷酸盐的排泄。
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.