Carbachol stimulates Cl- secretion via activation of two distinct apical Cl- pathways in cultured human T84 intestinal epithelial monolayers

Biochim Biophys Acta. 1994 Feb 17;1220(3):241-7. doi: 10.1016/0167-4889(94)90144-9.


The mode of action of carbachol in stimulation of transepithelial Cl- secretion in intact human intestinal T84 epithelial monolayers has been investigated in order to determine whether a DIDS-insensitive exit pathway (via CFTR) coexists with a DIDS-sensitive exit pathway at the apical membrane. Carbachol stimulates a transient inward Isc due to Cl- secretion whose magnitude is related to the basal level of inward Isc. The inward current responses to both carbachol and hypo-osmotic media are abolished in nominally Ca(2+)-free media. The action of apical DIDS (100 microM) upon carbachol-stimulated Isc depends on the initial value of the basal Isc. At basal Isc levels < 10 microA cm-2, 100 microM DIDS applied to the apical cell border abolishes the inward Isc following exposure to both carbachol and hypo-osmotic media. In contrast a VIP-stimulated inward Isc is observed in the presence of 100 microM DIDS. After VIP stimulation of inward Isc, or if spontaneous basal values of Isc were > 10 microA cm-2, the carbachol stimulation of inward Isc was largely insensitive to 100 microM DIDS. The data are consistent with the participation of both DIDS-sensitive and DIDS insensitive pathways for Cl- at the apical membrane of human intestinal T84 epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
  • Calcium / pharmacology
  • Carbachol / pharmacology*
  • Cell Line
  • Chlorides / metabolism*
  • Epithelium / drug effects
  • Epithelium / metabolism
  • Epithelium / physiology
  • Humans
  • Hypotonic Solutions
  • Intestines
  • Kinetics
  • Membrane Potentials
  • Time Factors
  • Vasoactive Intestinal Peptide / pharmacology


  • Chlorides
  • Hypotonic Solutions
  • Vasoactive Intestinal Peptide
  • Carbachol
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
  • Calcium