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Research ArticleArticle

Epidermal Growth Factor Protects Rat Epithelial Cells Against Acid-Induced Damage Through the Activation of Na+/H+ Exchangers

Osamu Furukawa, Hiroshi Matsui, Noriko Suzuki and Susumu Okabe
Journal of Pharmacology and Experimental Therapeutics February 1999, 288 (2) 620-626;
Osamu Furukawa
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Hiroshi Matsui
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Noriko Suzuki
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Susumu Okabe
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Abstract

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.

Footnotes

  • Send reprint requests to: Osamu Furukawa, Ph.D., Department of Applied Pharmacology, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan. E-mail:furukawa{at}mb.kyoto-phu.ac.jp

  • ↵1 Current address: Department of Gastroenterology, Institute of Clinical Medicine, Tsukuba University, 1–1-1, Tnnodai, Tsukuba, Ibaraki 305, Japan.

  • Abbreviations:
    BSA
    bovine serum albumin fraction V
    EGF
    epidermal growth factor
    PI-3 kinase
    phosphatidylinositol 3-kinase
    RT-PCR
    reverse transcription-polymerase chain reaction
    • Received February 2, 1998.
    • Accepted August 28, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 288 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 288, Issue 2
1 Feb 1999
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Research ArticleArticle

Epidermal Growth Factor Protects Rat Epithelial Cells Against Acid-Induced Damage Through the Activation of Na+/H+ Exchangers

Osamu Furukawa, Hiroshi Matsui, Noriko Suzuki and Susumu Okabe
Journal of Pharmacology and Experimental Therapeutics February 1, 1999, 288 (2) 620-626;

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Research ArticleArticle

Epidermal Growth Factor Protects Rat Epithelial Cells Against Acid-Induced Damage Through the Activation of Na+/H+ Exchangers

Osamu Furukawa, Hiroshi Matsui, Noriko Suzuki and Susumu Okabe
Journal of Pharmacology and Experimental Therapeutics February 1, 1999, 288 (2) 620-626;
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