Inhibitory effect of EGF on secretory response of rat parietal cells is associated with an induction of ODC.
The present studies were designed to evaluate the parietal cell acid production in response to short-time stimulation by epidermal growth factor (EGF). Studies were performed in vitro using isolated cells from rat stomachs, and acid production was indirectly determined by [14C]aminopyrine accumulation. EGF inhibited histamine-stimulated aminopyrine accumulation from standard incubation medium (K+ = 5 mM) but not from that with increased K+ concentration (K+ = 70 mM). EGF significantly stimulated ornithine decarboxylase (ODC) activity, an effect that was blocked by the specific ODC inhibitor, difluoromethylornithine (DFMO). In the presence of DFMO, EGF failed to inhibit histamine-stimulated aminopyrine uptake. Like EGF, the polyamine spermine, which is a direct product of enhanced ODC activity, also inhibited histamine-stimulated aminopyrine uptake. Unlike EGF, the spermine-induced inhibition of aminopyrine accumulation was not altered by DFMO. Thus the DFMO effect was specific to EGF. Taken together, these results are consistent with the postulate that EGF inhibits parietal cell secretory response through the induction of ODC activity and increased synthesis of polyamines.
Ostrowski
J
J
Department of Gastroenterology and Metabolism, Medical Center of Postgraduate Education, Warsaw, Poland.
Wojciechowski
K
K
Konturek
S J
SJ
Butruk
E
E
D000632:Aminopyrine / Q000493:pharmacokinetics; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D013096:Spermine / Q000494:pharmacology
D000632:Aminopyrine; D013096:Spermine; D004815:Epidermal Growth Factor; D006632:Histamine; D066246:ErbB Receptors; D009955:Ornithine Decarboxylase