Immunoreactive gastrin in differential and density gradient fractions of rat gastric mucosa.

Immunoreactive gastrin was measured in subcellular fractions of rat gastric mucosa. The sedimentational properties of subcellular gastrin-containing structures were distinct from those of mitochondria. After centrifugation in sucrose density gradients using a zonal rotor, the peak of immunoreactive gastrin was found in 1-17--1-18 g cm(-3) density sucrose (1-35 M; 39-5%, W/W). A thermolabile component with 125I-labelled gastrin-binding activity present in gastric mucosal homogenates and fractions was not associated with the gastrin storage vesicles sedimenting in density gradients.

The relationship of the serum gastrin and calcium concentrations in patients with multiple endocrine neoplasia type I.

The relationship between the serum gastrin and calcium concentrations has been examined in patients with multiple endocrine neoplasia type I. Variations in gastrin concentrations were induced by metiamide and secretin; calcium concentrations were altered by parathyroidectomy and by calcium infusion. Changes in the serum gastrin concentrations were not accompanied by changes in the serum calcium concentration. However, alteration of the serum calcium was accompanied by significant parallel changes in the serum gastrin. It is concluded that acute changes in the serum calcium may induce changes in the serum gastrin. Parathyroidectomy in these patients produced a fall in the serum gastrin, but the ability to produce large quantities of gastrin remains. It is postulated that the thyro-parathyroid hormones may modulate the relationship between calcium and gastrin.

The effect of sympathetic nerve stimulation on acid secretion, regional blood flows and oxygen usage by stomachs of anaesthetized cats.

1. Gastric acid secretion, and total gastric and mucosal blood flows (amidopyrine technique) were measured in anaesthetized cats. Oxygen contents of arterial and gastric venous blood were measured using an oximeter. 2. Splanchnic nerve stimulation (10 Hz) significantly reduced the acid output and total gastric and mucosal blood flows produced in response to maximal gastrin pentapeptide infusions. 3. The arterial haemoglobin concentration was significantly reduced during splanchnic nerve stimulation, and this is consistent with the hypothesis that the splanchnic nerve effect is directed against precapillary sphincters. 4. During the period of inhibition, gastric oxygen consumption and acid secretion were reduced to similar degrees. There was no significant change in oxygen extraction by the stomach. 5. It remains possible that the splanchnic nerves directly inhibit the parietal cell activity.

A possible origin of circulating gastrin component IV in cats.

1. Blood circulating in the cat is known to contain relatively large concentrations of gastrin components corresponding to Rehfeld's Components III and IV, whereas human blood has mostly Components II and III. 2. Synthetic cat gastrin 17NS was continuously injected into chloralose anaesthetized cats and at 1, 10 and 40 min after the start of injection there were significantly greater concentrations of immunoreactive gastrin Component IV than Component III in arterial blood (P less than 0.025 in each case). These concentrations were also greater than the total arterial gastrin concentration in the basal state. 3. Cat blood with EDTA incubated at 37 degrees C with synthetic cat and natural porcine gastrins 17NS produced Component IV. Hunan blood with EDTA incubated in a similar way with natural and synthetic human gastrins 17NS did not produce any detectable Component IV. Cat blood incubated with natural porcine and synthetic cat gastrin 17NS at 0 degrees C did not produce any Component IV. 4. We conclude that there may be an enzyme or enzymes in cat blood which cause the conversion of gastrin 17NS to Component IV.

Comparison of gastrin bioactivity and immunoreactivity of antral extracts from man, pig and cat.

1. The gastrin bioactivity and immunoreactivities of human, porcine and feline antral extracts were compared. 2. Human and porcine had similar activities but cat had much less. 3. The ratio of gastrin bioactivity to immunoreactivity was much greater with feline antral extracts than with human and porcine extracts.

The effect of sympathetic nerve stimulation on serum gastrin, gastric acid secretion and mucosal blood flow responses to meat extract stimulation in anaesthetized cats.

Chloralose anaesthetized cats were prepared with fundic and antral pouches. Fundic mucosal blood flow was measured by the amidopyrine technique and serum gastrin was measured by radioimmunoassay. 2. Meat extract suspension in the pyloric antrum produced a highly significant sixfold increase in arterial serum gastrin concentration (P less than 0-001). 3. The mean ratio of the fundic mucosal blood flow to acid secretory responses (deltaMBF/deltaH+ ratio) of 0-142 +/- 0-026 (25) ml./muequiv H+, is very similar to the values previously published for exogenous gastrin stimulation. 4. Splanchnic nerve stimulation, during responses to meat extract stimulation, produced significant reductions in gastric acid secretion (P less than 0-025), fundic mucosal blood flow (P less than 0-02), Arterial serum gastrin concentration (P less than 0-01) And gastrin delivered to the mucosa (P less than 0-001). 5. In the 30 min period following the end of splanchnic nerve stimulation only arterial serum gastrin concentration remained significantly reduced.

The effect of metramide on the prolonged serum gastrin response to feeding observed in patients with duodenal ulcer.

The response of serum gastrin to a meal has been studied in 11 normal subjects and 16 patients with duodenal ulceration. The mean serum gastrin concentration rises after a meal to similar peak values in both normal subjects and duodenal ulcer patients, and fall to basal values with 3 hours in normal subjects. In duodenal ulcer patients the peak concentration is sustained throughout the 3 hour test period, and this response is not affected by the administration of Metiamide. It is concluded that the control of gastrin release is defective in duodenal ulceration, and this may be due to a failure of the antral pH feedback mechanism. Gastrin may be a primary pathogenetic factor in duodenal ulceration.

Gastrin response to meals of different composition in normal subjects.

The serum gastrin responses and the integrated gastrin responses to eating three meals of very different composition were studied in the same normal subjects on different days. Two meals, a milk meal of 500 ml, and a breakfast of eggs, toast, butter, marmalade, fruit juice and coffee, were eaten at breakfast time. The serum gastrin responses to these meals were compared and contrasted with the concentrations observed when the subjects fasted over the same time of day. A steak meal was eaten at lunch time. There were no significant differences between the mean serum gastrin concentrations to the three meals but each meal produced a significant increase in serum gastrin above fasting levels. When the prefeeding gastrin concentration was subtracted from the gastrin responses then the integrated responses to the steak meal were greater than those to either of the breakfast meals. Considerable variability in response to any one meal was observed within the group of subjects, but those subjects who produced high serum gastrin concentrations to one meal did so to the others. Conversely, at low response to one meal was reflected in low responses to the other two meals. Fasting serum gastrin concentration was correlated with the age of the subject. Repeatability of the response to one meal was tested in two subjects who ate the same meal on four separate occasions showing their responses to be repeatable.

Comparison of vagal and meat stimulation on gastric acid secretion and serum gastrin.

The gastric acid secreted per unit of serum gastrin concentration or per unit of gastrin delivered to the gastric mucosa was significantly greater during electrical vagal stimulation than during stimulation by meat extract in the pyloric antrum. There was no significant difference in the concentrations of big, big gastrin or Components I and II in gastric venous serum during the two forms of stimulation. There were significantly greater concentrations of Components II and IV in gastric venous serum during meat extract stimulation than during vagal stimulation. The gastrin in gastric venous serum when meat extract was in the pyloric antrum was comprised of Component IV in addition to Component III whereas gastrin in extracts of cat antral mucosa was predominantly Component III. Gastric acid secretion in response to vagal stimulation was greater than can be accounted for by the action of gastrin alone and cannot be explained by differences in the known gastrin variants in the circulation during the two forms of stimulation.

The mechanism whereby growth hormone-release inhibiting hormone (somatostatin) inhibits food stimulated gastric acid secretion in the cat.

Growth hormone-release inhibiting hormone (somatostatin) inhibits the gastric acid response to food in concious cats. We have confirmed that this tetradecapeptide blocks the food stimulated gastrin release. However, the inhibition of gastrin release is delayed relative to that of acid secretion, &howing that the inhibition of food stimulated acid secretion is by primary effect on the acid secretory mechanism. No evidence was found of potentiation of either the gastric acid output or serum concentration of gastric in response to food.

Metiamide in the Zollinger-Ellison syndrome.

The histamine H2-receptor antagonist metiamide is an inhibitor of endogenous and stimulated gastric-acid secretion. It appears to have therapeutic possibilities in duodenal-ulcer disease. Three patients exhibiting the Zollinger-Ellison syndrome have been treated with this drug for six months or more. Rapid symptomatic improvement occurred in each case, followed by ulcer healing. There were also reductions in gastric secretion and consistent changes in the fasting serum-gastrin concentration. On patient relapsed temporarily during therapy. There have been no side effects. It is concluded that, in the short term, metiamide is of benefit in the Zollinger-Ellison syndrome.