Marks Joanne, Lee Grace J, Nadaraja Sobiya P, Debnam Edward S, Unwin Robert J
Department of Neuroscience, Physiology & Pharmacology, University College London, London, UK.
UCL Centre for Nephrology, University College London, London, UK.
Physiol Rep. 2015 Jan 27;3(1). doi: 10.14814/phy2.12281. Print 2015 Jan 1.
Despite the importance of extracellular phosphate in many essential biological processes, the mechanisms of phosphate transport across the epithelium of different intestinal segments remain unclear. We have used an in vitro method to investigate phosphate transport at the brush border membrane (BBM) of intact intestinal segments and an in vivo method to study transepithelial phosphate absorption. We have used micromolar phosphate concentrations known to favor NaPi-IIb-mediated transport, and millimolar concentrations that are representative of the levels we have measured in luminal contents, to compare the extent of Na(+)-dependent and Na(+)-independent phosphate transport along the rat duodenum, jejunum, ileum, and proximal and distal colon. Our findings confirm that overall the jejunum is the main site of phosphate absorption; however, at millimolar concentrations, absorption shows ~30% Na(+)-dependency, suggesting that transport is unlikely to be mediated exclusively by the Na(+)-dependent NaPi-IIb co-transporter. In the ileum, studies in vitro confirmed that relatively low levels of phosphate transport occur at the BBM of this segment, although significant Na(+)-dependent transport was detected using millimolar levels of phosphate in vivo. Since NaPi-IIb protein is not detectable at the rat ileal BBM, our data suggest the presence of an as yet unidentified Na(+)-dependent uptake pathway in this intestinal segment in vivo. In addition, we have confirmed that the colon has a significant capacity for phosphate absorption. Overall, this study highlights the complexities of intestinal phosphate absorption that can be revealed using different phosphate concentrations and experimental techniques.
尽管细胞外磷酸盐在许多重要生物过程中具有重要作用,但磷酸盐跨不同肠段上皮转运的机制仍不清楚。我们采用体外方法研究完整肠段刷状缘膜(BBM)处的磷酸盐转运,并采用体内方法研究跨上皮磷酸盐吸收。我们使用已知有利于NaPi-IIb介导转运的微摩尔磷酸盐浓度,以及代表我们在管腔内容物中测得水平的毫摩尔浓度,来比较大鼠十二指肠、空肠、回肠以及近端和远端结肠中Na⁺依赖性和非Na⁺依赖性磷酸盐转运的程度。我们的研究结果证实,总体上空肠是磷酸盐吸收的主要部位;然而,在毫摩尔浓度下,吸收显示约30%的Na⁺依赖性,这表明转运不太可能仅由Na⁺依赖性NaPi-IIb共转运体介导。在回肠,体外研究证实该段BBM处磷酸盐转运水平相对较低,尽管在体内使用毫摩尔水平的磷酸盐时检测到显著的Na⁺依赖性转运。由于在大鼠回肠BBM处未检测到NaPi-IIb蛋白,我们的数据表明在该肠段体内存在一种尚未确定的Na⁺依赖性摄取途径。此外,我们已经证实结肠具有显著的磷酸盐吸收能力。总体而言,这项研究突出了使用不同磷酸盐浓度和实验技术可揭示的肠道磷酸盐吸收的复杂性。