Hinkle K L, Samuelson L C
Department of Physiology, The University of Michigan, Ann Arbor, Michigan 48109-0622, USA.
Am J Physiol. 1999 Sep;277(3):G500-5. doi: 10.1152/ajpgi.1999.277.3.G500.
Gastrin is the principal hormonal inducer of gastric acid secretion. Chronic hypergastrinemia, leading to hypersecretion of gastric acid and increased proliferation of parietal and enterochromaffin-like (ECL) cells, has been well described. In contrast, the physiological consequences of chronic gastrin deficiency had been poorly understood until the recent genetic engineering of mouse mutants containing a gastrin gene deletion by homologous recombination in embryonic stem cells. This themes article describes the consequences of constitutive gastrin deficiency on the development and physiology of the stomach. A lack of gastrin disrupts basal gastric acid secretion and renders the acid secretory system unresponsive to acute histaminergic, cholinergic, and gastrinergic stimulation. The defect in acid secretion is greater than would have been predicted from previous studies in which gastrin action was acutely blocked. Cellular changes include thinning of the gastric mucosa in the gastrin-deficient mice, with a reduction in parietal cells and reduced expression of markers of parietal and ECL cell-differentiated functions. The results suggest that gastrin is required for the functional maturation of the acid-secretory system.
胃泌素是胃酸分泌的主要激素诱导物。慢性高胃泌素血症会导致胃酸分泌过多以及壁细胞和肠嗜铬样（ECL）细胞增殖增加，这一点已得到充分描述。相比之下，在通过胚胎干细胞中的同源重组对含有胃泌素基因缺失的小鼠突变体进行基因工程改造之前，人们对慢性胃泌素缺乏的生理后果了解甚少。这篇主题文章描述了组成型胃泌素缺乏对胃的发育和生理的影响。胃泌素的缺乏会扰乱基础胃酸分泌，并使胃酸分泌系统对急性组胺能、胆碱能和胃泌素能刺激无反应。胃酸分泌的缺陷比以往急性阻断胃泌素作用的研究预期的更大。细胞变化包括胃泌素缺乏小鼠的胃黏膜变薄，壁细胞减少，壁细胞和ECL细胞分化功能标志物的表达降低。结果表明，胃泌素是胃酸分泌系统功能成熟所必需的。
