Epidermal growth factor inhibits carbachol-stimulated canine parietal cell function via protein kinase C

被引:39
作者
Wang, LD [1 ]
Wilson, EJ [1 ]
Osburn, J [1 ]
DelValle, J [1 ]
机构
[1] UNIV MICHIGAN,DIV GASTROENTEROL,MED CTR,DEPT INTERNAL MED,ANN ARBOR,MI 48109
关键词
D O I
10.1053/gast.1996.v110.pm8566594
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background and Aims: Epidermal growth factor (EGF) inhibits secretagogue-stimulated gastric acid secretion via an EGF receptor located on parietal cells, The aim of this study was to examine whether this growth factor inhibited carbachol-stimulated acid secretion through a protein kinase C-dependent mechanism, Methods: The effect of EGF on carbachol-stimulated aminopyrine uptake, inositol trisphosphate formation, and intracellular Ca2+ ([Ca2+](i)) in purified cultured parietal cells was studied, The ability of protein kinase A and C inhibitors to alter the inhibitory action of EGF was assessed. EGF-mediated translocation and activation of protein kinase C in parietal cells were determined, Results: EGF dose dependently inhibited carbachol-stimulated aminopyrine uptake in a pertussis toxin-insensitive, genistein (tyrosine kinase inhibitor)-sensitive manner, with a maximal inhibitory effect (37.5% +/- 6.8%) achieved at 10(-7) mol/L. EGF did not significantly inhibit carbachol-stimulated inositol trisphosphate formation and did not alter the initial transient increase or sustained plateau in [Ca2+](i) stimulated by this secretagogue. The protein kinase C inhibitors H-7 and staurosporine dose dependently reversed the inhibitory action of EGF, whereas H-89 (protein kinase A inhibitor) failed to alter the effect of EGF, EGF pretreatment increased the translocation of alpha and beta(1) isoforms of protein kinase C and stimulated kinase activity in parietal cells, EGF did not down-regulate the parietal cell muscarinic receptor. Conclusions: The inhibitory action of EGF on carbachol-stimulated parietal cell activity seems to involve protein kinase C.
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页码:469 / 477
页数:9
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