Unique roles of G protein-coupled histamine H2 and gastrin receptors in growth and differentiation of gastric mucosa.
Unique roles of G protein-coupled histamine H2 and gastrin receptors in growth and differentiation of gastric mucosa.
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DOI：
10.1016/j.ejphar.2004.09.013
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发表时间：
2004-10
影响因子：
5
通讯作者：
Y. Fukushima;T. Matsui;T. Saitoh;M. Ichinose;K. Tateishi;T. Shindo;M. Fujishiro;H. Sakoda;N. Shojima;A. Kushiyama;S. Fukuda;M. Anai;Hiraku Ono;M. Oka;Y. Shimizu;H. Kurihara;R. Nagai;T. Ishikawa;T. Asano;M. Omata
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文献类型：
--
作者：
Y. Fukushima;T. Matsui;T. Saitoh;M. Ichinose;K. Tateishi;T. Shindo;M. Fujishiro;H. Sakoda;N. Shojima;A. Kushiyama;S. Fukuda;M. Anai;Hiraku Ono;M. Oka;Y. Shimizu;H. Kurihara;R. Nagai;T. Ishikawa;T. Asano;M. Omata
组胺H2受体和胃泌素受体的阻断对胃粘膜的生长有不同的影响，分别表现为肥大和萎缩。为了阐明胃泌素和组胺H2受体在胃粘膜中的作用，产生并分析了两者都缺乏的小鼠（双无效小鼠）。双无效小鼠表现出胃粘膜萎缩，显着的高胃泌素血症和较高的胃pH值比胃泌素受体无效的小鼠，甚至对卡巴胆碱无反应。比较10周龄野生型、组胺H2受体缺失、胃泌素受体缺失和双缺失小鼠的胃粘膜，揭示了这些受体在胃粘膜稳态中的独特作用。虽然小壁细胞和增加的数量和粘蛋白含量的粘液颈细胞是次要受损的酸生产，组胺H2受体负责主细胞成熟的胃蛋白酶原表达和III型粘蛋白。在双无效和胃泌素受体无效的小鼠，尽管胃粘膜萎缩，表面粘液细胞显着增加，与胃泌素无效的小鼠。因此，可以想象，在受刺激状态下，除胃泌素-17外的胃泌素基因产物可以独立于组胺H2受体对表面粘液细胞发挥增殖作用。这些发现提供了证据，不同的G蛋白偶联受体影响分化成不同的细胞谱系来自共同的干细胞在胃粘膜。
Disruption of histamine H2receptor and gastrin receptor had different effects growth of gastric mucosa: hypertrophy and atrophy, respectively. To clarify the roles of gastrin and histamine H2receptors in gastric mucosa, mice deficient in both (double-null mice) were generated and analyzed. Double-null mice exhibited atrophy of gastric mucosae, marked hypergastrinemia and higher gastric pH than gastrin receptor-null mice, which were unresponsive even to carbachol. Comparison of gastric mucosae from 10-week-old wild-type, histamine H2receptor-null, gastrin receptor-null and double-null mice revealed unique roles of these receptors in gastric mucosal homeostasis. While small parietal cells and increases in the number and mucin contents of mucous neck cells were secondary to impaired acid production, the histamine H2receptor was responsible for chief cell maturation in terms of pepsinogen expression and type III mucin. In double-null and gastrin receptor-null mice, despite gastric mucosal atrophy, surface mucous cells were significantly increased, in contrast to gastrin-null mice. Thus, it is conceivable that gastrin-gene product(s) other than gastrin-17, in the stimulated state, may exert proliferative actions on surface mucous cells independently of the histamine H2receptor. These findings provide evidence that different G-protein coupled-receptors affect differentiation into different cell lineages derived from common stem cells in gastric mucosa.