Epidermal growth factor enhances intracellular pH regulation via calcium signaling in acid-exposed primary cultured rabbit gastric epithelial cells.
We have elucidated the role of different ion transporters and epidermal growth factor(EGF) during luminal acid exposure in primary cultured rabbit surface epithelial cells by measuring intracellular calcium and pH. Amiloride, DIDS, or sodium or bicarbonate substitutions were used to inhibit ion transport. During luminal acid exposure the dominant intracellular pH regulator is the Na+/H+ antiport, and bicarbonate transport has only a secondary role, which is uncovered as the Na+/H+ function fails. The decrease in intracellular pH caused by luminal acid was significantly smaller in serosal EGF-treated epithelia than in controls. This defensive function of EGF was abolished by verapamil, BAPTA, and calmidazolium but not by TMB-8. EGF increased intracellular calcium, which was prevented by verapamil but not by TMB-8. EGF enhances gastric epithelial defense against luminal acid by inducing intracellular calcium signaling via plasma membrane verapamil-sensitive calcium channels and thereby enhancing the function of the Na+/H+ antiport.
Nylander-Koski
Outi
O
Department of Gastrointestinal Surgery, Helsinki University Central Hospital, Helsinki, Finland.
Mustonen
Harri
H
Puolakkainen
Pauli
P
Kiviluoto
Tuula
T
Kivilaakso
Eero
E
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects*
D004815:Epidermal Growth Factor; D002118:Calcium