INHIBITION OF ACID SECRETORY RESPONSE AND INDUCTION OF ORNITHINE DECARBOXYLASE AND ITS MESSENGER-RNA BY TGF-ALPHA AND EGF IN ISOLATED RAT GASTRIC GLANDS

TGF alpha shows structural and functional homology to EGF, but TGF alp ha'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 T GF alpha 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 t reatment with TGF alpha: and EGF had no effect on basal acid productio n but did inhibit histamine-stimulated acid production in a dose depen dent manner. The two growth factors did not inhibit histamine-stimulat ed aminopyrine (AP) uptake from incubation medium with concentration o f KCl increased from 5 to 70 mM. In the presence of specific ODC inhib itor, alpha-difluoromethylornithine (DFMO), both EGF and TGF alpha fai led to inhibit histamine-stimulated AP accumulation. Polyamine spermin e also inhibited AP accumulation but this inhibitory effect was not af fected by DFMO. After 1 h treatment with TGF alpha and EGF, ODC activi ties increased to an average 283 +/- 78% and 227 +/- 64% above the bas al activity, respectively. 30 min treatment of gastric glands with TGF alpha 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 quantita tively similar inhibitory effect on acid production and the induction of ODC activity or ODC mRNA by the two growth factors indicates that t he same mechanism(s) may affect acid secretory response, potentially l inking the inhibitory effect of TGF alpha and EGF with ODC activation.