Expression of the chromogranin A-derived peptides pancreastatin and WE14 in rat stomach ECL cells

被引:34
作者
Norlen, P
Curry, WJ
Chen, DA
Zhao, CM
Johnston, CF
Hakanson, R
机构
[1] LUND UNIV, DEPT PHARMACOL, S-22362 LUND, SWEDEN
[2] QUEENS UNIV BELFAST, DEPT MED, BELFAST BT12 6BJ, ANTRIM, NORTH IRELAND
关键词
immunohistochemistry; gastrin; omeprazole; chromatography; prohormone processing;
D O I
10.1016/S0167-0115(97)00021-9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The ECL cells constitute the predominant endocrine cell population in the mucosa of the acid-secreting part of the stomach (fundus). They are rich in chromogranin A (CGA), histamine and histidine decarboxylase (HDC). They secrete CGA-derived peptides and histamine in response to gastrin. The objective of this investigation was to examine the expression of pancreastatin (rat CGA(266-314)) and WE14 (rat CGA(343-356)) in rat stomach ECL cells. The distribution and cellular localisation of pancreastatin-and WE14-like immunoreactivities (LI) were analysed by radioimmunoassay and immunohistochemistry with antibodies against pancreastatin, WE,, and HDC. The effect of food deprivation on circulating pancreastatin-LI was examined in intact rats and after gastrectomy or fundectomy. Rats received gastrin-17 (5 nmol/kg/h) by continuous intravenous infusion ol omeprazole (400 mu mol/kg) once daily by the oral route, to induce hypergastrinemia. CGA-derived peptides in the ECL cells were characterised by gel permeation chromatography. The expression of CGA mRNA was examined by Northern blot analysis. Among all of the endocrine cells in the body, the ECL cell population was the richest in pancreastatin-LI, containing 20-25% of the total body content. Food deprivation and/or surgical removal of the ECL cells lowered the level of pancreastatin-LI in serum by about 80%. Activation of the ECL cells by gastrin infusion or omeprazole treatment raised the serum level of pancreastatin-LI, lowered the concentrations of pancreastatin-and WE14-LI in the ECL cells and increased the CGA mRNA concentration. Chromatographic analysis of the various CGA immunoreactive components in the ECL cells of normal and hypergastrinemic rats suggested that these cells respond to gastrin with a preferential release of the low-molecular-mass forms. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:121 / 133
页数:13
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