EGF promotes gastric mucosal restitution by activating Na(+)/H(+) exchange of epithelial cells.
This study was conducted to determine whether the contributions of epidermal growth factor (EGF) to gastric mucosal restitution after injury are mediated by stimulation of Na(+)/H(+) exchangers in surface mucous cells (SMC). Intact sheets of guinea pig gastric mucosae were incubated in vitro. Intracellular pH (pH(i)) in SMC was measured fluorometrically, using 2',7'- bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein. Restitution after Triton X-100-induced injury was evaluated by recovery of electrical resistance. At neutral luminal pH, exogenous EGF (ex-EGF) increased pH(i) and enhanced restitution in the absence but not in the presence of serosal HCO. During exposure to luminal acid, ex-EGF not only prevented intracellular acidosis but also promoted restitution. These effects of ex-EGF were blocked by serosal amiloride or anti-EGF-receptor antibody. In the absence of ex-EGF, restitution was inhibited by replacement of luminal and serosal solutions with fresh solutions and was blocked more completely by serosal anti-EGF-receptor antibody. These results suggest that both endogenous and ex-EGF contribute to restitution via basolateral EGF receptors, with effects mediated, at least in part, by stimulation of basolateral Na(+)/H(+) exchangers.
Yanaka
Akinori
A
Department of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. ynk-aki@md.tsukuba.ac.jp
Suzuki
Hideo
H
Shibahara
Takeshi
T
Matsui
Hirofumi
H
Nakahara
Akira
A
Tanaka
Naomi
N
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004234:Diuretics, Osmotic / Q000494:pharmacology; D017097:Electric Impedance; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism*; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D014316:Tritium; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D000906:Antibodies; D004232:Diuretics; D004234:Diuretics, Osmotic; D017923:Sodium-Hydrogen Exchangers; D014316:Tritium; D008353:Mannitol; D004815:Epidermal Growth Factor; D000584:Amiloride; D066246:ErbB Receptors