PT - JOURNAL ARTICLE AU - Osamu Furukawa AU - Hiroshi Matsui AU - Noriko Suzuki AU - Susumu Okabe TI - Epidermal Growth Factor Protects Rat Epithelial Cells Against Acid-Induced Damage Through the Activation of Na<sup>+</sup>/H<sup>+</sup> Exchangers DP - 1999 Feb 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 620--626 VI - 288 IP - 2 4099 - http://jpet.aspetjournals.org/content/288/2/620.short 4100 - http://jpet.aspetjournals.org/content/288/2/620.full SO - J Pharmacol Exp Ther1999 Feb 01; 288 AB - We examined the effect of epidermal growth factor (EGF) on acid-induced cell damage in rat gastric epithelial cells (RGM1) and investigated the mechanisms of this effect. Cells were incubated with EGF for 5, 15, 30, and 60 min, and then immersed in an acidified medium (pH 4.0) for 30 min to induce cell damage. EGF prevented cell damage in a concentration- and time-dependent manner. EGF reduced the effects of the acidified medium on the cells, preventing the reduction of intracellular pH. Replacement of Na+ with K+ in the acidified medium canceled the effect of EGF. Indomethacin and W-7 (a Ca-calmodulin inhibitor) did not alter the protective effect of EGF. In contrast, genistein (a tyrosine kinase inhibitor), amiloride (a Na+/H+ exchangers I and II inhibitor), and wortmannin (a phosphatidylinositol 3-kinase inhibitor) significantly decreased the effect of EGF. Expression of Na+/H+ exchangers type I and type II was confirmed by reverse transcription-polymerase chain reaction. Our results demonstrate that EGF prevents acid-induced cell damage, most likely through the activation of a Na+/H+exchanger II via phosphatidylinositol 3-kinase. The American Society for Pharmacology and Experimental Therapeutics