Transepithelial resistance can be regulated by the intestinal brush-border NA+/H+ exchanger NHE3

Jerrold R. Turner, Eric D. Black, Jeff Ward, Chung Ming Tse, Frederick A. Uchwat, Halima A. Alli, Mark Donowitz, James L. Madara, Jason M. Angle

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Initiation of intestinal Na+-glucose cotransport results in transient cell swelling and sustained increases in tight junction permeability. Since Na+/H+ exchange has been implicated in volume regulation after physiological cell swelling, we hypothesized that Na+/H+ exchange might also be required for Na+-glucose cotransport-dependent tight junction regulation. In Caco-2 monolayers with active Na+-glucose cotransport, inhibition of Na+/H+ exchange with 200 μM 5-(N,N-dimethyl)amiloride induced 36 ± 2% increases in transepithelial resistance (TER). Evaluation using multiple Na+/H+ exchange inhibitors showed that inhibition of the Na+/H+ exchanger 3 (NHE3) isoform was most closely related to TER increases. TER increases due to NHE3 inhibition were related to cytoplasmic acidification because cytoplasmic alkalinization with 5 mM NH4Cl prevented both cytoplasmic acidification and TER increases. However, NHE3 inhibition did not affect TER when Na+-glucose cotransport was inhibited. Myosin II regulatory light chain (MLC) phosphorylation decreased up to 43 ± 5% after inhibition of Na+/H+ exchange, similar to previous studies that associate decreased MLC phosphorylation with increased TER after inhibition of Na+-glucose cotransport. However, NHE3 inhibitors did not diminish Na+glucose cotransport. These data demonstrate that inhibition of NHE3 results in decreased MLC phosphorylation and increased TER and suggest that NHE3 may participate in the signaling pathway of Na+-glucose cotransport-dependent tight junction regulation.

Original languageEnglish (US)
Pages (from-to)C1918-C1924
JournalAmerican Journal of Physiology - Cell Physiology
Issue number6 48-6
StatePublished - 2000


  • Na-glucose cotransport
  • Na/H exchange
  • Tight junction regulation

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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