Giral Hector, Caldas Yupanqui, Sutherland Eileen, Wilson Paul, Breusegem Sophia, Barry Nicholas, Blaine Judith, Jiang Tao, Wang Xiaoxin X, Levi Moshe
Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Denver, and Veterans Affairs Medical Center, Aurora, CO 80045, USA.
Am J Physiol Renal Physiol. 2009 Nov;297(5):F1466-75. doi: 10.1152/ajprenal.00279.2009. Epub 2009 Aug 12.
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.
与慢性肾脏病相关的高磷血症是促进血管钙化的因素之一，而肠道磷（Pi）吸收是预防该病症的药理学靶点之一。II型钠-磷共转运体NaPi-2b是介导肠道磷重吸收的主要转运体。其他钠-磷转运体的潜在作用和调节机制仍不清楚。我们已经确定III型钠-磷共转运体PiT-1在肠上皮细胞顶端膜中的表达。钠-磷转运活性以及NaPi-2b和PiT-1蛋白主要在大鼠小肠的十二指肠和空肠中表达；它们在回肠中的表达可忽略不计。在慢性低磷饮食的情况下，空肠会出现适应性反应，刷状缘膜（BBM）钠-磷转运活性以及NaPi-2b蛋白和mRNA丰度增加，但PiT-1没有变化。然而，在大鼠从低磷饮食急性转换为高磷饮食后，十二指肠的BBM钠-磷转运活性增加，这与BBM NaPi-2b蛋白丰度增加有关。急性适应性上调仅限于十二指肠，并导致血清磷增加，从而产生短暂的餐后高磷血症。因此，我们的研究表明，十二指肠和空肠中钠-磷转运活性和NaPi-2b蛋白表达受到不同调节，餐后NaPi-2b的上调可能是治疗高磷血症的潜在靶点。
