Inhibition of acid secretory response and induction of ornithine decarboxylase and its mRNA by TGFα and EGF in isolated rat gastric glands

Abstract

TGFα shows structural and functional homology to EGF, but TGFα's mitogenic potency is greater. Our previous study showed that EGF may inhibit parietal cell secretory response through the induction of ornithine decarboxylase (ODC). The aim of this study was to determine parietal cell acid production in vitro in response to stimulation by TGFα and EGF and to compare the effect of these two growth factors on ODC activity and ODC mRNA in isolated rat gastric glands. 45 min treatment with TGFα and EGF had no effect on basal acid production but did inhibit histamine-stimulated acid production in a dose dependent manner. The two growth factors did not inhibit histamine-stimulated aminopyrine (AP) uptake from incubation medium with concentration of KCl increased from 5 to 70 mM. In the presence of specific ODC inhibitor, α-difluoromethylornithine (DFMO), both EGF and TGFα failed to inhibit histamine-stimulated AP accumulation. Polyamine spermine also inhibited AP accumulation but this inhibitory effect was not affected by DFMO. After 1 h treatment with TGFα and EGF, ODC activities increased to an average 283 ± 78% and 227 ± 64% above the basal activity, respectively. 30 min treatment of gastric glands with TGFα and EGF resulted in, respectively, 2.9 ± 0.4- and 2.7 ± 0.5-fold increases of ODC mRNA level, as assessed by RT-PCR. The quantitatively similar inhibitory effect on acid production and the induction of ODC activity or ODC mRNA by the two growth factors indicates that the same mechanism(s) may affect acid secretory response, potentially linking the inhibitory effect of TGFα and EGF with ODC activation.