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Biomedical subjects

D J Sanders

Publications and source records attributed to D J Sanders.

At least 55 records · Page 3Linked to original sources
PubMed1980

Gastric acid and pepsin-stimulating activity of non-sulphated fragments of gastrin in the cat.

The gastric acid and pepsin-stimulating activities of several C terminal fragments of non-sulphated human gastrin were investigated in the conscious cat prepared with cannulated gastric fistulae with a reproducible, continuous infusion method to construct dose-response curves. The gastric acid-stimulating activities were quantified by reference to the ED50 and were compared with the activity of synthetic non-sulphated human gastrin 17 (SHG17NS) and cat gastrin 17 (SCG17NS). SHG17NS had an ED50 of 0.329 nmol kg-1 h-1. SHG16NS, SHG15NS and SHG13NS all showed similar activities to SHG17NS. SCG17NS tested at low doses had similar activity to SHG17NS. SHG10NS, G5 and G4 and peptavlon showed progressively lower acid-stimulating activities: 26, 12, 9 and 9%, respectively, compared with SHG17NS. The gastric acid-stimulating activities of all the peptides were paralleled by similar pepsin-stimulating activities. The ratios of pepsin secretion:acid secretion were similar for all the peptides (1--2 microgram pepsin/microEq H+). The results are discussed in relation to the biological activity of the circulating gastrin components in the cat compared with other species and it is argued that component IV (corresponding to gastrin tetradecapeptide or minigastrin) is a major, physiologically active, circulating form of the hormone in the cat.

Animals↗
PubMed1980

Sensitivity of parietal cells to gastrin in the cat: comparison with man and dog.

The ED50 value for exogenous gastrin stimulation of gastric acid secretion in the cat is about 300 pmol kg-1h-1. Comparison with values in man and dog show that the ED50 value for gastrin in man is approximately 6-8 times lower than in cat or dog. The rise in circulating gastrin concentration during infusion of a standard dose of gastrin was 1,340 pg ml-1 in the conscious cat. Comparable studies in man and dog give values of 900 and 300 pg ml-1, respectively. Based on these observations, the sensitivity of the parietal cells to gastrin is in the order man, 1.0; dog, 0.47; and cat, 0.09.

Animals↗
PubMed1979

Effects of a combined oestrogen-progestin preparation on gastric acid and pepsin secretion, serum gastrin concentration and biliary secretion of bile acids, phospholipids, and cholesterol in the cat.

1 Daily ethinyloestradiol (50 mug) and norethisterone acetate (1 mg) treatment (Minovlar) was investigated on gastric acid and pepsin secretion, and fasting serum gastrin concentration in six conscious female cats prepared with chronic gastric fistulae. The effect on biliary secretion of bile acids, phospholipids, and cholesterol was investigated in three conscious female cats prepared with chronic gastric and intestinal fistulae, and cholecystectomy.2 Treatment for 49 days did not alter the gastric acid or pepsin response to either intravenous pentagastrin infusions or a food stimulus. The fasting serum gastrin concentration remained unaltered throughout the study.3 Treatment for 18 days did not alter the percentage concentration of cholesterol in the bile, but reduced the percentage concentration of phospholipid. This was mirrored by a rise in the percentage concentration of bile acids in the bile. These trends were quickly reversed on cessation of treatment.4 There was no sign of cholestasis associated with the treatment. Intestinal flow remained constant throughout the study, there was no lithocholic acid or other abnormal bile acids detectable in any samples, and there was no change in serum aspartate aminotransferase concentration.5 The results suggest that in female cats, treatment with a combined oestrogen-progestin preparation does not exert any beneficial effects on the aetiology of peptic ulceration through the reduction of acid or pepsin secretion, or the lowering of serum gastrin concentration. The preparation shows a tendency to produce more lithogenic bile, and this may partly explain the greater incidence of gall stones in women on the contraceptive pill.

Animals↗
PubMed1979

The effect of stimulation by meat on gastrins in pyloric antral mucosa of anaesthetized cats.

Chloralose anaesthetized cats were prepared with fundic and antral pouches. After stimulation with meat extract suspension in the antral pouches, the antral mucosae were collected, homogenized and subjected to subcellular fractionation to produce whole homogenates, debris, mitochondrial, granule and microsomal fractions and the cell supernatant. Total gastrin concentration and the quantities of gastrin components were measured in these cell fractions and compared with values obtained from a group of control animals which were not stimulated. Stimulation significantly increased the concentration of total gastrin in whole homogenates and in the cell supernatant. In whole homogenates the concentrations of gastrin components I, II, III and void volume gastrin all increased significantly after stimulation. In granules the concentration of Component III significantly increased. In microsomes the concentration of Componenet IV increased significantly. In cell supernatant the total amounts of Components III and IV increased significantly. It is concluded there was synthesis of gastrin under the experimental conditions used. The concentrations of those gastrin components which are larger than the predominant storage form (Component III) are increased and these larger components may be biosynthetic precursors. The significant increase in Component IV concentration in the cell supernatant and microsomes may suggest that Component IV is formed at least in part by antral tissue as well as by the known conversion process which occurs in cat blood.

Animals↗
PubMed1977

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.

Animals↗
PubMed1977

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.

Animals↗
PubMed1976

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.

Adult↗
PubMed1976

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.

Adult↗
PubMed1976

A review: the agents and actions of sympathetic nerve and catecholamine inhibition of gastric mucosal function.

The role of the sympathetic nerve supply to the gastric mucosa in gastric physiology is discussed. It is concluded that they are inhibitory to gastric acid secretion, mucosal blood flow, pepsin secretion, gastric oxygen consumption and that these nerves also decrease the serum gastrin concentration. Sympathetic nerve stimulation always reduces the mucosal blood flow and it is suggested therefore, that the inhibition of gastric secretion could be secondary to vasoconstriction mediated by noradrenaline release. The evidence for these conclusions is considered alongside the available histological evidence. It is concluded that the remaining hurdle is to place these phenomena within our knowledge of gastric physiology.

Animals↗
PubMed1976

Pepsin secretion in the anaesthetized cat and the effect of sympathetic nerve stimulation.

1. Experiments were performed on chloralose anaesthetized cats and gastric mucosal blood flow, acid and pepsin secretions were measured. Gastric mucosal pepsin and protein contents were measured at the end of the experiments which were done in three groups: gastrin (A), vagal (B), vagal and sympathetic nerve (C) stimulations. 2. Vagal stimulation significantly reduced (76%) the pepsin content of gastric mucosa compared with gastrin stimulated animals, none of which secreted pepsin. 3. The sum of the secreted and extracted pepsins for all the three groups was not significantly different. There was no significant difference in the extracted protein from any of the groups. 4. Gastric mucosal blood flow, acid and pepsin outputs all had significant correlations with time during the first 70 min of vagal stimulation. During the period 80-160 min of vagal stimulation acid secretion and mucosal blood flow were not correlated with time but pepsin output declined significantly. From 170 to 220 min of vagal stimulation, acid and pepsin outputs and mucosal blood flow were not correlated with time. 5. The assumed pepsin store during each period was calculated and after 40 min of vagal stimulation there is a constant percentage pepsin output from this assumed store. 6. There is some data to suggest that pepsinogen synthesis was occurring during the period 170-220 min of vagal stimulation. 7. Sympathetic nerve stimulation which started at 160 min after the beginning of sustained vagal stimulation, significantly inhibited gastric acid secretion and mucosal blood flow, and in addition it significantly inhibited pepsin secretion. This is consistent with the hypothesis that sympathetic nerve inhibition of gastric mucosal function is mediated by a vasoconstrictor mechanism.

Animals↗
PubMed1976

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.

Animals↗
PubMed1975

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.

Adult↗