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 journalArticle

Abstract

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)
JournalAmerican Journal of Physiology - Cell Physiology
Volume279
Issue number6 48-6
StatePublished - 2000

Fingerprint

Sodium-Hydrogen Antiporter
Brushes
Microvilli
Glucose
Phosphorylation
Tight Junctions
Acidification
Swelling
Myosin Type II
Myosin Light Chains
Monolayers
Permeability
Protein Isoforms

Keywords

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

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Turner, J. R., Black, E. D., Ward, J., Tse, C. M., Uchwat, F. A., Alli, H. A., ... Angle, J. M. (2000). Transepithelial resistance can be regulated by the intestinal brush-border NA+/H+ exchanger NHE3. American Journal of Physiology - Cell Physiology, 279(6 48-6).

Transepithelial resistance can be regulated by the intestinal brush-border NA+/H+ exchanger NHE3. / Turner, Jerrold R.; Black, Eric D.; Ward, Jeff; Tse, Chung Ming; Uchwat, Frederick A.; Alli, Halima A.; Donowitz, Mark; Madara, James L.; Angle, Jason M.

In: American Journal of Physiology - Cell Physiology, Vol. 279, No. 6 48-6, 2000.

Research output: Contribution to journalArticle

Turner, Jerrold R. ; Black, Eric D. ; Ward, Jeff ; Tse, Chung Ming ; Uchwat, Frederick A. ; Alli, Halima A. ; Donowitz, Mark ; Madara, James L. ; Angle, Jason M. / Transepithelial resistance can be regulated by the intestinal brush-border NA+/H+ exchanger NHE3. In: American Journal of Physiology - Cell Physiology. 2000 ; Vol. 279, No. 6 48-6.
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