pancreastatin and Hyperplasia

The role of enterochromaffin-like (ECL) cells in gastric carcinogenesis is not fully understood. Spontaneous tumours developing in hypergastrinemic female cotton rats have an adenocarcinoma phenotype, but numerous cells in the dysplastic mucosa as well as in the carcinomas are positive for neuroendocrine markers. In the present study of female cotton rats with 2 and 8 months' hypergastrinemia, the oxyntic mucosa of the stomach was examined histologically and immunolabelled for histidine decarboxylase (HDC) and pancreastatin, and hyperplastic and neoplastic ECL cells were evaluated by electron microscopy. These animals developed hyperplasia of the oxyntic mucosa in general and of the ECL cells in particular after 2 months and dysplasia and carcinomas after 8 months. The immunoreactivity of the ECL cells in the oxyntic mucosa was increased at 2 months and declined at 8 months. These histological changes were associated with progressive loss of secretory vesicles and granules in ECL cells. We suggest that ECL cells in hypergastrinemic cotton rats dedifferentiate with time and that the gastric carcinomas may develop from ECL cells.

Topics: Animals; Carcinoma; Cell Transformation, Neoplastic; Chromogranin A; Enterochromaffin-like Cells; Female; Gastrins; Histidine Decarboxylase; Hyperplasia; Pancreatic Hormones; Parietal Cells, Gastric; Rats; Sigmodontinae; Stomach Neoplasms

ECL cells in the oxyntic mucosa secrete histamine and pancreastatin in response to gastrin. The present study examined gastrin-evoked ECL-cell responses over a 10-week time span in terms of individual ECL cells and unit ECL cell volume. Rats were treated with omeprazole (400 micromol/kg per day orally). The concentrations of gastrin and pancreastatin in serum and of histamine and pancreastatin in the oxyntic mucosa were measured as was the activity of the oxyntic mucosal histidine decarboxylase (HDC). The ECL cells were visualized by immunostaining of histamine and examined by electron microscopy. The total ECL cell number and volume, and the mean ECL cell diameter and volume were determined. The HDC, chromogranin A (CGA) and cholecystokinin-B (CCK-B) receptor mRNA concentrations were determined. In terms of individual ECL cells and unit ECL cell volume, the serum pancreastatin concentration, the oxyntic mucosal histamine content, HDC activity, and HDC, CGA and CCK-B receptor mRNA contents increased slowly at first and then leveled off or started to decline after 2 weeks. After 10 weeks all ECL-cell parameters (expressed per unit ECL cell volume) were back to or approaching the starting value. In conclusion, sustained hypergastrinemia first activates each individual ECL cell (with a peak after 1-2 weeks) and then causes gradual functional impairment, the activity returning towards the pre-stimulation level.

Topics: Animals; Base Sequence; Cell Size; Chromogranin A; Chromogranins; Enterochromaffin-like Cells; Enzyme Inhibitors; Gastric Mucosa; Gastrins; Histamine Release; Histidine Decarboxylase; Hyperplasia; Male; Microscopy, Electron; Omeprazole; Pancreatic Hormones; Parietal Cells, Gastric; Rats; Rats, Sprague-Dawley; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; RNA, Messenger; Stomach