Epidermal growth factor inhibits carbachol-stimulated canine parietal cell function via protein kinase C

Gastroenterology. 1996 Feb;110(2):469-77. doi: 10.1053/gast.1996.v110.pm8566594.


Background & aims: Epidermal growth factor (EGF) inhibits secretagogue-stimulated gastric acid secretion via an EGF receptor located on parietal cells. The aim of this study was to examine whether this growth factor inhibited carbachol-stimulated acid secretion through a protein kinase C-dependent mechanism.

Methods: The effect of EGF on carbachol-stimulated aminopyrine uptake, inositol trisphosphate formation, and intracellular Ca2+ ([Ca2+]i) in purified cultured parietal cells was studied. The ability of protein kinase A and C inhibitors to alter the inhibitory action of EGF was assessed. EGF-mediated translocation and activation of protein kinase C in parietal cells were determined.

Results: EGF dose dependently inhibited carbachol-stimulated aminopyrine uptake in a pertussis toxin-insensitive, genistein (tyrosine kinase inhibitor)--sensitive manner, with a maximal inhibitory effect (37.5% +/- 6.8%) achieved at 10(-7) mol/L. EGF did not significantly inhibit carbachol-stimulated inositol trisphosphate formation and did not alter the initial transient increase or sustained plateau in [Ca2+]i stimulated by this secretagogue. The protein kinase C inhibitors H-7 and staurosporine dose dependently reversed the inhibitory action of EGF, whereas H-89 (protein kinase A inhibitor) failed to alter the effect of EGF. EGF pretreatment increased the translocation of alpha and beta 1 isoforms of protein kinase C and stimulated kinase activity in parietal cells. EGF did not down-regulate the parietal cell muscarinic receptor.

Conclusions: The inhibitory action of EGF on carbachol-stimulated parietal cell activity seems to involve protein kinase C.

Publication types

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

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Alkaloids / pharmacology
  • Aminopyrine / pharmacokinetics
  • Animals
  • Calcium / metabolism
  • Carbachol / pharmacology*
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Dogs
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Epidermal Growth Factor / pharmacology*
  • Gastric Acid / metabolism
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Isoquinolines / pharmacology
  • Parasympathomimetics / pharmacology*
  • Parietal Cells, Gastric / drug effects*
  • Parietal Cells, Gastric / metabolism
  • Parietal Cells, Gastric / physiology
  • Piperazines / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Receptors, Muscarinic / metabolism
  • Staurosporine
  • Sulfonamides*


  • Alkaloids
  • Enzyme Inhibitors
  • Isoquinolines
  • Parasympathomimetics
  • Piperazines
  • Receptors, Muscarinic
  • Sulfonamides
  • Aminopyrine
  • Epidermal Growth Factor
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Inositol 1,4,5-Trisphosphate
  • Carbachol
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Staurosporine
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
  • Calcium