Abstract
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.
Highlights
Phosphate homeostasis is maintained by mechanisms that mediate and control phosphate transport across the renal and intestinal epithelium
Information as fundamental as the phosphate level found in intestinal luminal contents is not readily available. This has led to most studies of intestinal phosphate handling employing phosphate concentrations of 0.1 mmol/L to reflect the affinity of intestinal brush border membrane (BBM) vesicles for phosphate documented in the early studies (Berner et al 1976; Loghman-Adham et al 1987), and the known kinetic characteristics of NaPi-IIb when expressed in oocytes (Hilfiker et al 1998; Forster et al 2006)
Based on the luminal phosphate concentrations observed in rats fed a normal maintenance diet, we examined the effect of millimolar phosphate levels in the uptake buffer on Na+-dependent and Na+-independent phosphate transport
Summary
Phosphate homeostasis is maintained by mechanisms that mediate and control phosphate transport across the renal and intestinal epithelium. In the steady state the kidneys excrete phosphate at the same rate as that absorbed by the small intestine. Despite our detailed knowledge of the mechanisms and regulation of renal phosphate transport in the kidney, we know far less about the pathways responsible for phosphate absorption across the intestinal tract. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
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