Multiple actions of epidermal growth factor and TGF-alpha on rabbit gastric parietal cell function

Am J Physiol. 1994 Nov;267(5 Pt 1):G818-26. doi: 10.1152/ajpgi.1994.267.5.G818.


Parietal cells in primary culture and freshly isolated parietal cells were used to compare acute and chronic effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) on acid-secretory related activity, measured as accumulation of the weak base, [14C]aminopyrine (AP). EGF and TGF-alpha chronically enhanced basal and agonist-stimulated AP accumulation (mean effective concentration 0.6-0.8 nM) but acutely inhibited responses to histamine and carbachol (half-maximal inhibitory concentration approximately 4 nM). Pertussis toxin (250 ng/ml, 4 h) suppressed acute EGF inhibition of histamine-stimulated AP accumulation but not the chronic enhancement. A subclass of tyrosine kinase inhibitors suppressed chronic EGF effects (genistein > tyrphostin B56 >>> tyrphostin B42), whereas tyrphostin A25, lavendustin A, and the inactive genistein analogue, daidzein, had no significant effect. In contrast, histamine-stimulated AP accumulation was acutely potentiated by genistein, daidzein, and tyrphostin B42, but not tyrphostin B56. Reduced phosphorylation of a 44- to 45-kDa protein with an isoelectric point of approximately 7 [phosphoprotein (pp) 44] was correlated with chronic inhibition but not with acute potentiation by specific tyrosine kinase inhibitors. Preliminary data indicate that pp44 is a member of the mitogen-activated protein kinase family of tyrosine/threonine kinases (also known as extracellular signal-related kinases). We propose that 1) EGF and/or TGF-alpha modulates parietal cell function by multiple signaling pathways, 2) a soluble tyrosine kinase may be involved in the mediation of the chronic effects of EGF, and 3) acute potentiation of histamine-stimulated AP accumulation by certain tyrosine kinase inhibitors and daidzein is probably not mediated by receptor-associated tyrosine kinases.

Publication types

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

MeSH terms

  • Aminopyrine / pharmacokinetics
  • Animals
  • Dinoprostone / antagonists & inhibitors
  • Dose-Response Relationship, Drug
  • Epidermal Growth Factor / pharmacology*
  • Male
  • Parietal Cells, Gastric / drug effects*
  • Parietal Cells, Gastric / physiology
  • Pertussis Toxin
  • Phosphoproteins / metabolism
  • Phosphorylation / drug effects
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Rabbits
  • Time Factors
  • Transforming Growth Factor alpha / pharmacology*
  • Virulence Factors, Bordetella / pharmacology


  • Phosphoproteins
  • Transforming Growth Factor alpha
  • Virulence Factors, Bordetella
  • Aminopyrine
  • Epidermal Growth Factor
  • Pertussis Toxin
  • Protein-Tyrosine Kinases
  • Dinoprostone