Salganik R I, Bersimbaev R I, Argutinskaya S V, Kiseleva E V, Khristolyubova N B, Deribas V I
Mol Cell Biochem. 1976 Sep 30;12(3):181-91. doi: 10.1007/BF01741716.
The regulation patterns of gastric acid secretion in rats were investigated. Pentagastrin and histamine stimulate gastric acid secretion, but the inhibitors of DNA-dependent synthesis of RNA and of proteins prevent only the pentagastrin action. It has been found that pentagastrin induces histidine decarboxylase in gastric mucosa, ensuring local accumulation of histamine. The latter activates adenylate cyclase and results in 3',5'-AMP accumulation in gastric tissues. The administration of pentagastrin, histamine or 3',5'-AMP enhances the activity of gastric carbonic anhydrase, the enzyme which takes part in HCl formation. The data suggest that these three compounds act sequentially (pentagastrin leads to histamine leads to3',5'-AMP) and the effect of the last one could be mediated through 3',5'-AMP dependent protein kinase. The experiments in vitro demonstrated that gastric carbonic anhydrase can be separated into two isoenzymes and thephosphorylation of one of them by the 3',5'-AMP dependent protein kinase sharply increases its activity. The findings raise the possibility that histamine and 3',5'-AMP, mediating gastrin action, form together with enzymes (histidine decarboxylase, adenylate cyclase, protein kinase, carbonic anhydrase) a caascade of amplifiers. Autoradiographic studies have shown that [3H]-pentagastrin is not bound by oxyntic cells but adheres preferentially to histamine-producing alpha-like endocrine cells and to the chief cells, while 3H-histamine adheres preferentially to oxyntic and to chief cells. Electron microscopy indicates that only pentagastrin (but not histamine) initiates in alpha-like endocrine cells ultrastructural changes characteristic for induction. Pentagastrin, histamine and 3',5'-AMP administration produces in oxyntic cells ultrastructural changes typical for the secretion processes. These results lead to assumption that pentagastrin (gastrin) induces histidine decarboxylase in alpha-like endocrine cells of gastric glands. Histamine which is secreted enhances adenylate cyclase activity in the neighbouring oxyntic cells where 3',5'-AMP dependent protein kinase activates carbonic anhydrase by means of phosphorylation. These different cells form, probably, a multicellular functional unit for gastric acid secretion.
研究了大鼠胃酸分泌的调节模式。五肽胃泌素和组胺刺激胃酸分泌，但依赖DNA的RNA和蛋白质合成抑制剂仅能阻止五肽胃泌素的作用。已发现五肽胃泌素可诱导胃黏膜中的组氨酸脱羧酶，从而确保组胺在局部蓄积。组胺激活腺苷酸环化酶，导致胃组织中3',5'-AMP蓄积。给予五肽胃泌素、组胺或3',5'-AMP可增强胃碳酸酐酶的活性，该酶参与盐酸的形成。数据表明这三种化合物依次发挥作用（五肽胃泌素导致组胺导致3',5'-AMP），且最后一种化合物的作用可能通过依赖3',5'-AMP的蛋白激酶介导。体外实验表明，胃碳酸酐酶可分为两种同工酶，依赖3',5'-AMP的蛋白激酶对其中一种同工酶的磷酸化可使其活性急剧增加。这些发现提示，介导胃泌素作用的组胺和3',5'-AMP可能与酶（组氨酸脱羧酶、腺苷酸环化酶、蛋白激酶、碳酸酐酶）共同形成一个放大级联。放射自显影研究表明，[3H] - 五肽胃泌素不与壁细胞结合，而是优先黏附于产生组胺的α样内分泌细胞和主细胞，而3H - 组胺则优先黏附于壁细胞和主细胞。电子显微镜检查表明，只有五肽胃泌素（而非组胺）能在α样内分泌细胞中引发诱导特有的超微结构变化。给予五肽胃泌素、组胺和3',5'-AMP会在壁细胞中产生分泌过程特有的超微结构变化。这些结果导致推测，五肽胃泌素（胃泌素）可诱导胃腺α样内分泌细胞中的组氨酸脱羧酶。分泌的组胺可增强相邻壁细胞中的腺苷酸环化酶活性，在这些壁细胞中，依赖3',5'-AMP的蛋白激酶通过磷酸化激活碳酸酐酶。这些不同的细胞可能形成了一个用于胃酸分泌的多细胞功能单元。
