Inhibition of acid secretory response and induction of ornithine decarboxylase and its mRNA by TGF alpha and EGF in isolated rat gastric glands.
TGF alpha shows structural and functional homology to EGF, but TGF alpha'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 TGF 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 treatment with TGF alpha 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, alpha-difluoromethylornithine (DFMO), both EGF and TGF alpha 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 TGF alpha 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 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Wojciechowski
K
K
Department of Gastroenterology and Metabolism, Medical Center of Postgraduate Education, Warszawa, Poland.
Trzeciak
L
L
Konturek
S J
SJ
Ostrowski
J
J
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D000518:Eflornithine / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000502:physiology; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009955:Ornithine Decarboxylase / Q000096:biosynthesis* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D017931:DNA Primers; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D000632:Aminopyrine; D013096:Spermine; D004815:Epidermal Growth Factor; D006632:Histamine; D009955:Ornithine Decarboxylase; D000518:Eflornithine