Histamine secretion from rat enterochromaffinlike cells.
Histamine secretion from rat enterochromaffinlike cells.
复制标题
大鼠肠嗜铬样细胞分泌组胺。
DOI：
10.1016/0016-5085(93)90719-s
复制
发表时间：
1993
期刊：
影响因子：
29.4
通讯作者：
Sachs,G
中科院分区：
文献类型：
--
作者：
Prinz,C;Kajimura,M;Scott,DR;Mercier,F;Helander,HF;Sachs,G
背景：体内研究表明，胃肠嗜铬细胞（ECL）在调节胃酸分泌中起重要作用。缺乏这种功能的直接证据，需要制备高度纯化的ECL细胞。本研究利用纯化的大鼠基底粘膜ECL细胞，探讨了ECL细胞释放组胺在酸分泌的外周调节中的可能作用和机制。方法：采用洗脱和密度梯度离心相结合的方法纯化大鼠基底细胞ECL。富集是通过含有V型腺苷三磷酸酶的酸性液泡、电子显微镜、免疫染色和组胺含量和释放来确定的。结果：ECL细胞相对于基底上皮至少富集65倍。胃泌素（EC500.2 nmol/L）和胆囊收缩素八肽（EC500.04 nmol/L）以时间和剂量依赖的方式刺激组胺释放，提示CCK- b受体亚型，CCK- b拮抗剂L365,260抑制胃泌素/CCK刺激。生长抑素也抑制胃泌素介导的组胺释放。单细胞显像显示胃泌素双相升高胞浆内钙浓度。碳二醇和C激酶激活剂120- tetradecanoylphorbol13 -acetate也刺激组胺释放。肾上腺素（被心得安阻断）、福斯克林和二丁基-5′-环腺苷单磷酸也有效，暗示β-肾上腺素能通路。h3激动剂R-α-甲基组胺抑制，而h3拮抗剂硫哌丁胺增强胃泌素/CCK刺激组胺释放。结论：这些体外实验结果支持ECL细胞在胃酸分泌的外周调节中起核心作用。
Background:In vivo studies have suggested an important role for gastric enterochromaffinlike (ECL) cells in mediating acid secretion. Direct evidence for this function is lacking and requires a preparation of highly purified ECL cells. This work investigates the possible role and mechanism of histamine release from the ECL cell in the peripheral regulation of acid secretion, using purified ECL cells from rat fundic mucosa.Methods:A combination of elutriation and density-gradient centrifugation was used to purify rat fundic ECL cells. Enrichment was determined by the presence of acidic vacuoles containing a V type adenosine triphosphatase, electron microscopy, immunostaining, and histamine content and release.Results:ECL cells were enriched at least 65-fold with respect to the fundic epithelium. Gastrin (EC500.2 nmol/L) and cholecystokinin octapeptide (nonsulfated, EC500.04 nmol/L) stimulated histamine release in a time- and dose-dependent manner, suggesting a CCK-B receptor subtype, confirmed by the inhibition of gastrin/CCK stimulation with the CCK-B antagonist L365,260. Somatostatin also inhibited gastrin-mediated histamine release. Single cell imaging showed that gastrin elevated intracellular cytosolic calcium concentration biphasically. Carbachol and the C kinase activator 120-tetradecanoylphorbol-13-acetate also stimulated histamine release. Epinephrine (blocked by propranolol), forskolin, and dibutyryl-5′-cyclic adenosine monophosphate were also effective, implicating a β-adrenergic pathway. The H3agonist R-α-methyl-histamine inhibited, whereas the H3-antagonist thioperamide potentiated gastrin/CCK stimulated histamine release.Conclusions:These in vitro results support a central role for the ECL cell in the peripheral regulation of gastric acid secretion.