MULTIPLE ACTIONS OF EPIDERMAL GROWTH-FACTOR AND TGF-ALPHA ON RABBIT GASTRIC PARIETAL-CELL FUNCTION

被引:50
作者
CHEW, CS
NAKAMURA, K
PETROPOULOS, AC
机构
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 1994年 / 267卷 / 05期
关键词
AMINOPYRINE ACCUMULATION; INSULIN-LIKE GROWTH FACTOR I; TYROSINE KINASES; PROTEIN PHOSPHORYLATION; HISTAMINE; CARBACHOL; GASTRIN; DIBUTYRYL ADENOSINE 3'; 5'-CYCLIC MONOPHOSPHATE; CIMETIDINE; PROSTAGLANDIN E(2); PERTUSSIS TOXIN; INTRACELLULAR CALCIUM;
D O I
10.1152/ajpgi.1994.267.5.G818
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Multiple actions of epidermal growth factor and TGF-alpha on rabbit gastric parietal cell function. Am. J. Physiol. 267 (Gastrointest. Liver Physiol. 30): G818-G826, 1994.-Parietal cells in primary culture and freshly isolated parietal cells were used to compare acute and chronic effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) on acid-secretory related activity, measured as accumulation of the weak base, [C-14]aminopyrine (AP). EGF and TGF-alpha chronically enhanced basal and agonist-stimulated AP accumulation (mean effective concentration 0.6-0.8 nM) but acutely inhibited responses to histamine and carbachol (half-maximal inhibitory concentration similar to 4 nM). Pertussis toxin (250 ng/ml, 4 h) suppressed acute EGF inhibition of histamine-stimulated AP accumulation but not the chronic enhancement. A subclass of tyrosine kinase inhibitors suppressed chronic EGF effects (genistein > tyrphostin B56 >>> tyrphostin B42), whereas tyrphostin A25, lavendustin A, and the inactive genistein analogue, daidzein, had no significant effect. In contrast, histamine-stimulated AP accumulation was acutely potentiated by genistein, daidzein, and tyrphostin B42, but not tyrphostin B56. Reduced phosphorylation of a 44- to 45-kDa protein with an isoelectric point of similar to 7 [phosphoprotein (pp) 44] was correlated with chronic inhibition but not with acute potentiation by specific tyrosine kinase inhibitors. Preliminary data indicate that pp44 is a member of the mitogen-activated protein kinase family of tyrosine/threonine kinases (also known as extracellular signal-related kinases). We propose that 1) EGF and/or TGF-alpha modulates parietal cell function by multiple signaling pathways, 2) a soluble tyrosine kinase may be involved in the mediation of the chronic effects of EGF, and 3) acute potentiation of histamine-stimulated AP accumulation by certain tyrosine kinase inhibitors and daidzein is probably not mediated by receptor-associated tyrosine kinases.
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收藏
页码:G818 / G826
页数:9
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