Phosphatidic acid modulates Cl- secretion in T84 cells: varying effects depending on mode of stimulation

Am J Physiol. 1993 May;264(5 Pt 1):C1210-8. doi: 10.1152/ajpcell.1993.264.5.C1210.


Cl- secretion in T84 cells evoked by a stimulus that activates protein kinase C, carbachol, was associated with elevated levels of 32P-labeled phosphatidic acid (PA). PA's role in the regulation of Cl- secretion was explored by examining the effect of exogenous PA (10(-4) M) on Cl- secretion and intracellular Ca2+ levels ([Ca2+]i) in monolayers. PA potentiated the effect of carbachol on [Ca2+]i and Cl- secretion, although it did not stimulate Cl- secretion by itself. PA had divergent effects on cyclic nucleotide-dependent Cl- secretion. It delayed Cl- secretion induced by vasoactive intestinal polypeptide [VIP, adenosine 3',5'-cyclic monophosphate (cAMP) dependent] but potentiated that induced by the heat-stable enterotoxin of Escherichia coli (STa; guanosine 3',5'-cyclic monophosphate dependent). PA did not alter AMP or GMP levels, suggesting that PA acts at a site distal to the generation of these second messengers. PA caused a slight increase in phosphorylation of protein kinase C substrates but not of cAMP-dependent protein kinase substrates. However, PA is probably not acting through a classical protein kinase C pathway, because we have previously shown that phorbol esters inhibit carbachol's actions, and the protein kinase C inhibitor staurosporine failed to block the effect of PA on VIP- or STa-stimulated Cl- secretion. Thus PA differentially regulates stimulated Cl- secretion in T84 cells, depending on the nature of the agonist.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcium / metabolism*
  • Carbachol / pharmacology
  • Chlorides / metabolism*
  • Chromatography, Thin Layer
  • Colonic Neoplasms
  • Cyclic AMP / metabolism
  • Cytosol / metabolism
  • Electrophoresis, Gel, Two-Dimensional
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Inositol Phosphates / isolation & purification
  • Inositol Phosphates / metabolism*
  • Kinetics
  • Phosphatidic Acids / metabolism*
  • Phosphatidic Acids / pharmacology*
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositols / metabolism
  • Phospholipids / metabolism*
  • Phosphoproteins / isolation & purification
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Tumor Cells, Cultured
  • Vasoactive Intestinal Peptide / pharmacology


  • Chlorides
  • Inositol Phosphates
  • Phosphatidic Acids
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositols
  • Phospholipids
  • Phosphoproteins
  • Vasoactive Intestinal Peptide
  • Carbachol
  • Cyclic AMP
  • Calcium