INDUCTION OF HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH-FACTOR AND AMPHIREGULIN MESSENGER-RNAS 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 a re expressed in response to gastrin in rat stomach, Rat gastrin-17I (2 .5 nmol/kg/hour) or gastrin-17I plus gastrin receptor antagonist, L-74 0,093 (2.0 mg/kg/hour), was injected intravenously into male Sprague-D awley rats. RNA was extracted from oxyntic mucosa, and heparin-binding epidermal growth factor-like growth factor and related peptide gene e xpression was estimated using a ribonuclease protection assay, The lev el of transforming growth factor-alpha mRNA did not change at any time point during the experiment. In contrast, the levels of heparin-bindi ng epidermal growth factor-like growth factor and amphiregulin mRNA we re significantly increased within 3 hours following gastrin infusion a nd reached maximum levels 6 and 12 hours later, respectively, Continuo us infusion of gastrin significantly increased oxyntic mucosal prolife ration, Gastrin receptor antagonist significantly inhibited gastrin-in duced heparin-binding epidermal growth factor-like growth factor and a mphiregulin gene expression and gastrin-induced oxyntic mucosal. proli feration. These findings indicate that heparin-binding epidermal growt h factor-like growth factor and amphiregulin genes are induced by gast rin and that they play a role in the trophic action of gastrin on oxyn tic mucosa. (C) 1997 Academic Press.