gastrin-17 and Hyperplasia

Studies in gastrin-deficient mice have demonstrated critical roles for gastrin peptides in the regulation of gastric acid secretion, but the relative contributions of amidated (G-17) and glycine-extended (G17-Gly) gastrin remain unclear. We examined the effects of these 2 forms of gastrin on acid secretion in gastrin-deficient mice.. Sixty gastrin-deficient mice received infusions of saline, or 1, 6, or 14 days of amidated gastrin 17 (G-17), G17-Gly, or both G-17 and G17-Gly at 10 nmol. kg(-1). h(-1). Twenty-four gastrin-deficient mice were then infused for 14 days with 1, 2, or 5 nmol. kg(-1). h(-1) of G-17 or G-17 and G17-Gly. Acid secretion was determined 4 hours after pyloric ligation, and gastric tissue was processed for histology, immunohistochemistry, and electron microscopy.. Infusion of G-17 increased acid secretion in a dose-dependent manner with a peak at 5 nmol. kg(-1). h(-1) and a subsequent decrease in acid secretion at higher doses. Infusion of G17-Gly alone had no effect on acid secretion, but coinfusion with G-17 resulted in significantly higher levels of acid secretion at all doses examined than infusion with G-17 alone. The potentiating effect of G17-Gly on G-17-induced acid secretion was associated with increased parietal cell activation but was independent of changes in parietal and enterochromaffin-like cell number, fundic proliferation rates, and H(+),K(+)-adenine triphosphatase expression. G17-Gly also prevented the formation of vacuolar canaliculi and lipofuscin bodies in the parietal cells induced by G-17.. G17-Gly appears to synergize with G-17 to up-regulate acid secretion and prevent parietal cell degradation. These results suggest that G17-Gly plays an important role in parietal cell function.

Topics: Animals; Cell Division; Drug Synergism; Gastric Acid; Gastric Mucosa; Gastrins; H(+)-K(+)-Exchanging ATPase; Hyperplasia; Mice; Mice, Knockout; Parietal Cells, Gastric; Stomach

To determine if gastrin in hyperparathyroid glands is true gastrin or artifact and to determine the frequency of gastrin in parathyroid glands, 20 parathyroid glands from 11 patients with hyperparathyroidism but without MEA were extracted and analyzed for gastrin. The parathyroid glands from 4 out of 11 patients had measurable gastrin immunoreactivity (10.7 + 6 pg/mg tissue). Column separation chromatography confirmed that this was true gastrin (40% G-34; 50% G-17). Immunohistochemistry with ABC (avidin biotin complex) immunoperoxidase confirmed the presence of gastrin in cytoplasmic vesicles in scattered parathyroid cells. True gastrin does exist in some cells in some patients with hyperparathyroidism.

Topics: Adenoma; APUD Cells; Gastrins; Humans; Hyperparathyroidism; Hyperplasia; Immunoenzyme Techniques; Parathyroid Glands; Parathyroid Neoplasms; Protein Precursors; Radioimmunoassay