Ichikawa T, Ishihara K, Kusakabe T, Kurihara M, Kawakami T, Takenaka T, Saigenji K, Hotta K
Department of Biochemistry, Kitasato University School of Medicine, Sagamihara, Japan.
Am J Physiol. 1998 Jan;274(1):G138-46. doi: 10.1152/ajpgi.1998.274.1.G138.
Although gastrin, histamine, and carbachol (CCh) accelerate gastric mucin metabolism, information about their target cells of mucin production is lacking. To clarify this, we examined the effects of these stimulants, including the possible participation of nitric oxide (NO), on mucin biosynthesis in distinct sites and layers of rat gastric mucosa. Pieces of tissue obtained from the corpus and antrum were incubated in a medium containing radioactive precursors and each stimulant, with or without NO synthase (NOS) inhibitor. Distribution of NOS was compared with that of the specific mucins by immunostaining using specific antiserum and monoclonal antibodies. In the full-thickness corpus mucosa, tetragastrin enhanced [3H]glucosamine incorporation into mucin but had no effect on [14C]threonine incorporation. Both histamine and CCh dose dependently increased 3H- and 14C-labeled corpus mucin. Only CCh stimulated antral mucin biosynthesis. CCh stimulation was noted in the corpus mucosa after removal of surface mucous cells, but stimulation by tetragastrin or histamine disappeared as a result of this pretreatment. Only tetragastrin-induced activation was completely blocked by the NOS inhibitor. NOS immunoreactivity was limited to surface mucous cells. Mucus-producing cells present in the different sites and layers of the gastric mucosa have distinct mechanisms for regulation of mucin biosynthesis. Gastrin-stimulated mucin biosynthesis mediated by NO is limited to surface mucous cells of rat gastric oxyntic mucosa.
尽管胃泌素、组胺和卡巴胆碱(CCh)可加速胃黏液代谢,但关于它们在黏液产生方面的靶细胞信息却很缺乏。为阐明这一点,我们研究了这些刺激物,包括一氧化氮(NO)可能的参与情况,对大鼠胃黏膜不同部位和层次黏液生物合成的影响。从胃体和胃窦获取的组织块在含有放射性前体和每种刺激物的培养基中孵育,同时添加或不添加一氧化氮合酶(NOS)抑制剂。通过使用特异性抗血清和单克隆抗体进行免疫染色,将NOS的分布与特异性黏液进行比较。在胃体全层黏膜中,四肽胃泌素增强了[3H]葡糖胺掺入黏液的过程,但对[14C]苏氨酸掺入没有影响。组胺和CCh均剂量依赖性地增加了胃体中3H和14C标记的黏液。只有CCh刺激了胃窦黏液的生物合成。去除表面黏液细胞后,胃体黏膜中可观察到CCh刺激,但四肽胃泌素或组胺的刺激因这种预处理而消失。只有四肽胃泌素诱导的激活被NOS抑制剂完全阻断。NOS免疫反应性仅限于表面黏液细胞。胃黏膜不同部位和层次的黏液产生细胞在黏液生物合成的调节机制上存在差异。由NO介导的胃泌素刺激的黏液生物合成仅限于大鼠胃泌酸黏膜的表面黏液细胞。