Induction of heparin binding epidermal growth factor-like growth factor and amphiregulin mRNAs by gastrin in the rat stomach.
The present study was designed to investigate whether heparin-binding epidermal growth factor-like growth factor and its related peptides are expressed in response to gastrin in rat stomach. Rat gastrin-17I (2.5 nmol/kg/hour) or gastrin-17I plus gastrin receptor antagonist, L-740,093 (2.0 mg/kg/hour), was injected intravenously into male Sprague-Dawley rats. RNA was extracted from oxyntic mucosa, and heparin-binding epidermal growth factor-like growth factor and related peptide gene expression was estimated using a ribonuclease protection assay. The level of transforming growth factor-alpha mRNA did not change at any time point during the experiment. In contrast, the levels of heparin-binding epidermal growth factor-like growth factor and amphiregulin mRNA were significantly increased within 3 hours following gastrin infusion and reached maximum levels 6 and 12 hours later, respectively. Continuous infusion of gastrin significantly increased oxyntic mucosal proliferation. Gastrin receptor antagonist significantly inhibited gastrin-induced heparin-binding epidermal growth factor-like growth factor and amphiregulin gene expression and gastrin-induced oxyntic mucosal proliferation. These findings indicate that heparin-binding epidermal growth factor-like growth factor and amphiregulin genes are induced by gastrin and that they play a role in the trophic action of gastrin on oxyntic mucosa.
Tsutsui
S
S
Second Department of Internal Medicine, Osaka University Medical School, Suita, Japan. Shusaku_Tsutsui@msn.com
Shinomura
Y
Y
Higashiyama
S
S
Higashimoto
Y
Y
Miyazaki
Y
Y
Kanayama
S
S
Hiraoka
S
S
Minami
T
T
Kitamura
S
S
Murayama
Y
Y
Miyagawa
J
J
Taniguchi
N
N
Matsuzawa
Y
Y
D066258:Amphiregulin; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D018076:DNA, Complementary; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000096:biosynthesis*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000008:administration & dosage / Q000494:pharmacology*; D006023:Glycoproteins / Q000096:biosynthesis*; D006133:Growth Substances / Q000096:biosynthesis*; D006493:Heparin / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D007262:Infusions, Intravenous; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D008297:Male; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism; D010671:Phenylurea Compounds / Q000494:pharmacology; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic / Q000187:drug effects*
D066258:Amphiregulin; C587850:Areg protein, rat; D001570:Benzodiazepinones; D018076:DNA, Complementary; D066255:EGF Family of Proteins; D005755:Gastrins; D006023:Glycoproteins; D006133:Growth Substances; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D010671:Phenylurea Compounds; D015347:RNA Probes; D012333:RNA, Messenger; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C090649:L 740093; D004815:Epidermal Growth Factor; D006493:Heparin