ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2013
The Na⁺/H⁺ exchanger isoform 3 is required for active paracellular and transcellular Ca²⁺ transport across murine cecum.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 44 citations in OpenAlex.
- Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability.Science translational medicine · 2018Trial
- Functional maturation of preterm intestinal epithelium through CFTR activation.Communications biology · 2025Article
- Claudin-12: guardian of the tissue barrier or friend of tumor cells.Tissue barriers · 2025Review
- Ion channels and transporters regulate nutrient absorption in health and disease.Journal of cellular and molecular medicine · 2023Review
- Vitamin D and malabsorptive gastrointestinal conditions: A bidirectional relationship?Reviews in endocrine & metabolic disorders · 2023Review
- Maternal Epidermal Growth Factor Promotes Neonatal Claudin-2 Dependent Increases in Small Intestinal Calcium Permeability.Function (Oxford, England) · 2023Article
- Claudin-2 and claudin-12 form independent, complementary pores required to maintain calcium homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The role of NHE3 (Slc9a3) in oxalate and sodium transport by mouse intestine and regulation by cAMP.Physiological reports · 2021Article
- Segmental differences in Slc26a3-dependent ClThe journal of physiological sciences : JPS · 2021Article
- Claudin-2 deficiency associates with hypercalciuria in mice and human kidney stone disease.The Journal of clinical investigation · 2020Article
- Claudin-12 Knockout Mice Demonstrate Reduced Proximal Tubule Calcium Permeability.International journal of molecular sciences · 2020Article
- Factors inhibiting intestinal calcium absorption: hormones and luminal factors that prevent excessive calcium uptake.The journal of physiological sciences : JPS · 2019Review
- Intestinal phosphate absorption: The paracellular pathway predominates?Experimental biology and medicine (Maywood, N.J.) · 2019Article
- Activation of the calcium sensing receptor attenuates TRPV6-dependent intestinal calcium absorption.JCI insight · 2019Article
- TRPV6 and CaCellular and molecular gastroenterology and hepatology · 2019Article
- Intestinal absorption and renal reabsorption of calcium throughout postnatal development.Experimental biology and medicine (Maywood, N.J.) · 2017Review
- Effects of phospho- and calciotropic hormones on electrolyte transport in the proximal tubule.F1000Research · 2017Review
- Deficiency of Carbonic Anhydrase II Results in a Urinary Concentrating Defect.Frontiers in physiology · 2017Article
- Carbonic anhydrase II binds to and increases the activity of the epithelial sodium-proton exchanger, NHE3.American journal of physiology. Renal physiology · 2015Article
- Traditional and emerging roles for the SLC9 Na+/H+ exchangers.Pflugers Archiv : European journal of physiology · 2014Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Intestinal calcium (Ca²⁺) absorption occurs via paracellular and transcellular pathways. Although the transcellular route has been extensively studied, mechanisms mediating paracellular absorption are largely unexplored. Unlike passive diffusion, secondarily active paracellular Ca²⁺ uptake occurs against an electrochemical gradient with water flux providing the driving force. Water movement is dictated by concentration differences that are largely determined by Na⁺ fluxes. Consequently, we hypothesized that Na⁺ absorption mediates Ca²⁺ flux. NHE3 is central to intestinal Na⁺ absorption. NHE3 knockout mice (NHE3-/-) display impaired intestinal Na⁺, water, and Ca²⁺ absorption. However, the mechanism mediating this latter abnormality is not clear. To investigate this, we used Ussing chambers to measure net Ca²⁺ absorption across different segments of wild-type mouse intestine. The cecum was the only segment with net Ca²⁺ absorption. Quantitative RT-PCR measurements revealed cecal expression of all genes implicated in intestinal Ca²⁺ absorption, including NHE3. We therefore employed this segment for further studies. Inhibition of NHE3 with 100 μM 5-(N-ethyl-N-isopropyl) amiloride decreased luminal-to-serosal and increased serosal-to-luminal Ca²⁺ flux. NHE3-/- mice had a >60% decrease in luminal-to-serosal Ca²⁺ flux. Ussing chambers experiments under altered voltage clamps (-25, 0, +25 mV) showed decreased transcellular and secondarily active paracellular Ca²⁺ absorption in NHE3-/- mice relative to wild-type animals. Consistent with this, cecal Trpv6 expression was diminished in NHE3-/- mice. Together these results implicate NHE3 in intestinal Ca(2+) absorption and support the theory that this is, at least partially, due to the role of NHE3 in Na⁺ and water absorption.
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