J. F. Rehfeld

Effect of antrum exclusion on endocrine cells of rat stomach.

1. Following antrum exclusion the serum gastrin concentration was raised and independent of the prandial state. The antral gastrin concentration and number of gastrin cells were greatly lowered. 2. The histamine content and the number of histamine‐storing endocrine (entero‐chromaffin‐like) cells in the oxyntic mucosa was almost doubled and the mucosal histidine decarboxylase activity was greatly elevated following antrum exclusion. 3. At the ultrastructural level both types of histamine‐storing endocrine cells (ECL and A‐like) were found to be enlarged and to have a reduced number of granules per unit cytoplasm. These changes are compatible with an increased secretory activity. The G (gastrin) cells were not increased in size but their granule volume density was lowered. 4. We propose that antrum exclusion results in uninhibited gastrin release causing profound changes in the histamine‐storing endocrine cells of the oxyntic mucosa. The cells respond to the hypergastrinemia by an increase in functional activity (activation of histidine decarboxylase and reduction of granule volume density) as well as by an increase in number and size.

The life cycle of the gastrin granule

SummaryThe ultrastructure of gastrin cells in the rat antrum was analyzed with standardized and quantitative planimetric methods. Resting and active cells were compared. The gastrin cells were activated by removal of the acidproducing part of the stomach (fundectomy). As a result the serum gastrin concentrations were greatly elevated. Compared with gastrin cells in fasted control rats the gastrin cells in fundectomized rats were increased in number, contained fewer cytoplasmic granules, increased amount of endoplasmic reticulum, and an enlarged Golgi area.Generally, the secretory granules of the gastrin cell displayed a wide range of electron density from highly electron-dense to electron-lucent. They exhibited certain characteristic features: 1) Electron-dense granules made up a greater proportion of the total granule population in active gastrin cells than in resting cells. 2) Electron-dense granules were more frequent near the Golgi stacks than in the periphery of the cell. 3) Electron-dense granules were smaller in size than the electron-lucent granules; hence, small electron-dense granules probably represent young granules (progranules), while large, electron-lucent granules represent mature (old) granules. 4) Electron-dense granules invariably displayed a more intense immunoreactivity than electron-lucent granules.The gastrins are generated from a large precursor molecule. The posttranslational processing of this precursor is reflected in the gastrin-component pattern. The gastrin-component pattern in antral extracts of fundectomized and normal fasting rats differed in that the proportion of the gastrin-4-like component was reduced, whereas the gastrin-34-like component was increased in the fundectomized rats. The results suggest a greater proportion of small gastrin components in the mature granules than in the newly formed ones, presumably due to more extensive conversion of larger forms into smaller forms with a longer granule half-life. As a result gastrin-17-and gastrin-34-like components make up a larger proportion of total gastrin in active gastrin cells than in resting gastrin cells.

Antro-pyloric gastrinoma associated with pancreatic nesidioblastosis and proliferation of islets

An adenoma in the antropyloric mucosa of a patient with recurrent duodenal ulcers was identified by immunofluorescence as a gastrinoma. Resected pancreatic tissue showed greatly increased numbers of islets and ducts. Insulin and glucagon cells were revealed by immunofluorescence not only in the islets but also in the duct epithelium. Signs suggesting neoformation of islets from the duct epithelium were observed.

Gastrin cell proliferation after chronic stimulation: effect of vagal denervation or gastric surgery in the rat.

Chronic stimulation of the antral gastrin cells by elevated antral pH was achieved by fundectomy, antrum exclusion, fundectomy plus antrum exclusion, antrocolic transposition, and vagal denervation plus pyloroplasty. For comparison we studied also the effects of pyloroplasty alone and of portacaval shunting. All operations that elevated the antral pH resulted in high gastrin concentrations in serum. Particularly high concentrations were observed in fundectomized rats. Vagal denervation of fundectomized or antrum excluded rats reduced the serum gastrin concentration slightly compared with the corresponding innervated animals. Portacaval shunting reduced the gastrin concentration in serum. The antral gastrin concentration was raised or unchanged following fundectomy and vagal denervation, and reduced following antrum exclusion, antrum exclusion plus vagotomy, fundectomy plus antrum exclusion, fundectomy plus vagotomy, antrocolic transposition and portacaval shunt. The gastrin cell density in the antral mucosa was raised following fundectomy, vagotomy, and fundectomy plus vagotomy, unchanged following fundectomy plus antrum exclusion and antrocolic transposition, and reduced following antrum exclusion and portacaval shunting. Ultrastructurally the gastrin (G) cells in the excluded antrum and in the antrum of fundectomized rats showed signs of secretory activity in that the granule volume density or the number of granules per unit cytoplasm was lowered. In the fundectomized rats moreover, the endoplasmic reticulum of the G cells was increased, the Golgi area enlarged and the proportion and volume density of electron dense granules greatly increased. The granule profile diameter was not affected by either antrum exclusion or fundectomy. The results on the excluded antrum indicate that elevated antral pH per se is not sufficient to produce gastrin cell proliferation. In the fundectomized rats, where the hyperlasia of antral gastrin cells was considerable, there is the added stimulus of ingested food. In fundectomized plus antrum excluded rats this stimulus is eliminated and no proliferation ensues. The passage of intestinal material, as in the rats subjected to antrocolic transposition, did not elicit gastrin cell proliferation which seems to suggest that the character of the luminal material is important. We propose therefore that gastrin cell proliferation is due to the combined stimulation of high antral pH and passage of food. Vagal innervation is not required.

Occurrence and neonatal development of gastrin immunoreactivity in the digestive tract of the rat

SummaryThe distribution of gastrin immunoreactivity in the rat gut was examined by immunochemical and immunohistochemical techniques. Gastrin occurs predominantly in the antrum proper, but gastrin is found also in the adjacent part of the oxyntic mucosa and in the duodenum. In the remainder of the gut the gastrin concentration is very low. No gastrin cells and very low gastrin concentrations are observed in the antrum at birth. The gastrin concentration as well as the number of gastrin cells increases progressively with age. The antral gastrin concentration reaches adult or near-adult values 30–40 days after birth.

Gastric acid response to pylorus ligation in rats: is gastrin or histamine involved?

1. Pylorus ligation stimulated the acid output in vagally intact rats. The serum gastrin concentration and the gastric mucosal histamine content were not affected. The gastric histidine decarboxylase activity was initially slightly elevated and then greatly reduced (12‐20 hr after ligation).

Immunofluorescent localization of gastrin in rabbit antropyloric mucosa to argyrophil cells exhibiting formaldehyde-ozone-induced fluorescence

SummaryThe cellular localization of gastrin in the rabbit pyloric antrum was established by immunofluorescence. The gastrin cell was argyrophil (Grimelius technique) and identical with a previously described cell type that emits fluorescence upon combined formaldehydeozone treatment, a feature that has been interpreted as indicating storage of peptides with NH2-terminal tryptophan. The identity of the peptides and its relation to gastrin is unknown.

Gastrin: Obligatory intermediate in the postprandial mobilization of gastric histamine in the rat

In unoperated fasted rats, feeding raised the serum gastrin concentration, reduced the gastric mucosal histamine content and activated the gastric histidine decarboxylase. The reduction of gastric histamine and activation of histidine decarboxylase was induced also by the injection of pentagastrin. In antrectomized rats, feeding failed to produce these effects. Injection of pentagastrin, however, still lowered gastric histamine and activated gastric histidine decarboxylase. Thus, antral gastrin seems to be an obligatory mediator of the postprandial activation of histidine decarboxylase and mobilization of histamine.

Importance of the kidneys for gastrin elimination and gastric function.

1. The gastrin concentrations in serum were elevated after nephrectomy in rats and mice indicating the importance of the kidney for elimination of gastrin in these species. In guinea‐pigs and rabbits nephrectomy did not cause increased serum gastrin concentrations. In rats there was a gradual rise in the serum gastrin level up to 48 hr after bilateral nephrectomy and also after ureteral ligation. After the latter operation the concentrations of gastrin in serum were lower than after nephrectomy. Significant elevation of the gastrin level 48 hr after ureteral ligation indicates that gastrin is eliminated at least partly through glomerular filtration. The gastric histidine decarboxylase activity after nephrectomy or ureteral ligation generally reflected the concentration of circulating gastrin.

Effect of deglycyrrhizinized liquorice on gastric acid secretion, histidine decarboxylase activity and serum gastrin level in the rat

Nachweis, dass die Behandlung mit einem deglycyrrhizinierten Lakrizpräparat die basale Säurereaktion bei Ratten hemmt. Erhöhtes antrales pH führt zu vermehrter Freisetzung von antralem Gastrin mit bedeutender Aktivierung der Histidindecarboxylase in der Magenschleimhaut.