TGF-alpha reduces bradykinin-stimulated ion transport and prostaglandin release in human colonic epithelial cells

Am J Physiol. 1999 Apr;276(4):C848-55. doi: 10.1152/ajpcell.1999.276.4.C848.

Abstract

The effect of chronic exposure to transforming growth factor-alpha (TGF-alpha) on bradykinin-stimulated acute prostanoid production and ion secretion in monolayers of HCA-7 colony 29 colonic epithelial cells has been studied. Monolayers synthesized prostaglandin E2 (PGE2) at a basal rate of 2.10 +/- 0.31 pg. monolayer-1. min-1 over 24 h. Bradykinin (10(-8)-10(-5) M) dose dependently increased acute PGE2 release by three orders of magnitude. This was associated with a rise in cAMP from 1.60 +/- 0.14 to 2.90 +/- 0.1 pmol/monolayer (P < 0.02) and a dose-dependent increase in short-circuit current (SCC). When monolayers were primed by a 24-h exposure to TGF-alpha, basal PGE2 release rose to 6.31 +/- 0.38 pg. monolayer-1. min-1 (TGF-alpha concn 10 ng/ml; P = 0.001). However, the stimulation of acute prostaglandin release, intracellular cAMP, and increased SCC by bradykinin was significantly reduced by preincubation with TGF-alpha. Priming with PGE2 (10(-8)-10(-6) M) over 24 h mimicked the effect of TGF-alpha on bradykinin-induced changes in cAMP and SCC. These data suggest that enhanced chronic release of prostaglandins in response to stimulation with TGF-alpha may downregulate acute responses to bradykinin. In vivo, TGF-alpha could have an important modulatory function in regulating secretion under inflammatory conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonic Acid / pharmacology
  • Bradykinin / pharmacology*
  • Carbachol / pharmacology
  • Cell Line
  • Chlorides / metabolism*
  • Colforsin / pharmacology
  • Colon
  • Cyclic AMP / metabolism
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Dinoprostone / biosynthesis*
  • Dinoprostone / pharmacology
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / physiology*
  • Isoenzymes / metabolism*
  • Kinetics
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Proteins
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Time Factors
  • Transforming Growth Factor alpha / pharmacology*
  • Transforming Growth Factor alpha / physiology

Substances

  • Chlorides
  • Isoenzymes
  • Membrane Proteins
  • Transforming Growth Factor alpha
  • Colforsin
  • Arachidonic Acid
  • Carbachol
  • Cyclic AMP
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • Bradykinin