Heidenhain Pouch Dogs Research Articles

Activity of 2-(5-methyl-4-imidazolyl)-ethylamine (5-methylhistamine) on the gastric secretion of different laboratory animals and of man

The compound 2-(5-methyl-4-imidazolyl)-ethylamine, namely 5-methylhistamine3(5-MeH), was compared to histamine for its stimulant activity on gastric secretion in Heidenhain pouch dogs, cats, rats and also on gastric secretion of human volunteers. In dogs and cats 5-MeH had approximately the same activity as histamine, both as regards threshold doses and peak secretory effects, when given by subcutaneous injection or by intravenous infusion. In the rat 5-MeH was 60% less active than histamine when given by either i.v. injection or infusion. In the preliminary experiments carried out in man, 5-MeH and histamine given at the same doses had approximately the same effect as regards volume, acidity of the gastric juice and also persistence of effect. 5-MeH was tolerated in all the subjects whereas histamine was not tolerated in 1 out of 5 subjects. The results obtained suggest that this new methyl derivative could reprent a good alternative to thmmon stimulants used in the clinical gastric secretory tests.

The gastric antisecretory activity of pyridyl-2-thioacetamide (CMN 131).

A thiocarboxamide derivative, pyridyl-2-thioacetamide, referred to as CMN 131, was characterized for its gastric antisecretory properties in rats and dogs. Its activity was first determined in 4-hr pylorus-ligated rats and in gastric fistula rats under basal and carbachol-stimulated (18 μg/kg/hr s.c.) conditions. ED50 of acid output inhibition was 1.46 (0.92–2.31) mg/kg by intraduodenal route and 3.85 (2.65–5.59) mg/kg s.c. respectively. The activity was further confirmed in Heidenhain-pouch dogs whose gastric secretion was stimulated by pentagastrin (3.20 μg/kg/hr i.v.) and histamine (160 μg/kg/hr i.v.). Under all these conditions, CMN 131 in doses ranging from 1 to 10 mg/kg, whatever the drug administration route, possesses a long-acting antisecretory property characterized first by an activity on acid concentration and second by an equal inhibitory potency on histamine and pentagastrin stimulation.

The influence of bile on canine gastric secretion

The effect of various types of biliary diversion on the daily secretion of Heidenhain pouches in dogs was studied. Total external diversion of bile brought about a decrease in gastric secretion while simple internal diversion of bile to the distal gut via Roux-en-Y segment caused significant increase in Heidenhain pouch secretion; the observed increases in secretion could not be accounted for on the basis of impairment of liver function as measured by serial BSP determinations.

Release of gastric inhibitor from the intestine of dogs infused intravenously with sodium oleate.

We found previously that intravenous infusion of sodium oleate induced inhibition of pentagastrin-stimulated gastric secretion in canine Heidenhain pouches. In the present study we attempted to verify the hypothesis that such intravenous infusion provoked Extract of intestinal mucosa release, from intestinal mucosa, of an enterogastrone-like inhibitor. Lyophilized extracts of canine intestinal secretion or mucosa were prepared using dogs infused for 6 h with saline or with sodium oleate. These extracts weren then assayed for their inhibitory action by intravenous infusion into Heidenhain pouches of dogs, stimulated with pentagastrin. When solvent or extracts prepared from intestinal juice or gut mucosa of dogs infused with saline were tested, no inhibition of gastric acid occurred. When extracts prepared from dogs infused with oleate were assayed, gastric acid secretion was inhibited. We concluded that intravenous infusion of fat results in the release of a gastric inhibitor of intestinal origin which behaves as an enterogastrone. This may be a most reasonable explanation of the action of intravenous sodium oleate on gastric secretion.

Dopamine in human gastric juice determined by a sensitive double-isotope-derivative technique.

Dopamine was measured in human gastric juice by a sensitive enzymatic double-isotope-derivative technique. Two normal subjects and two patients with a duodenal ulcer were examined before and after injection of peptavlon. Four subjects who had previously undergone a selective gastric vagotomy were studied before and after injection of insulin. During basal conditions human gastric juice dopamine concentration averaged 5.41 ± 1.67 ng/ml (± S.D.). There was no change in gastric juice dopamine after stimulation with peptavlon or insulin. In other experiments dopamine was measured in the secretion from Heidenhain pouches in dogs. The dopamine concentration in the fasting secretion was approximately the same as that observed in man. After food stimulation in the main stomach the total amount of dopamine secreted from the Heidenhain pouches increased considerably, mainly due to an eight- to fourteen-fold increase in dopamine concentration. Dopamine in peripheral venous blood in the dogs did not change during foo...

Augmentation of pentagastrin stimulated gastric secretion in the Heidenhain pouch dog by amodiaquine: inhibition of histamine methyltransferase in vivo?

In 9 dogs, whose maximum gastric acid response to pentagastrin was evoked by 6 μg/kg, the total gastric secretion as well as the peak gastric secretion was enhanced by amodiaquine. The optimum dose of this antimalarial drug was 2 mg/kg, whereas 0.25 mg/kg were without effect and 3 mg/kg reduced already the augmentation of gastric secretion by this substance. The increase in acid output by amodiaquine was greater than that in volume. The total secretion was more enhanced than the peak secretion, which means a longer duration of the amodiaquine potentiated gastric secretion elicited by pentagastrin, than that without application of amodiaquine contrary to that stimulated by exogenous histamine. Amodiaquine itself did not stimulate gastric acid secretion, in contrast to prostigmine and carbachol. Thus amodiaquine seemed not to enhance gastric secretion by a direct or indirect parasympathomimetic action. The question whether amodiaquine acted on gastric secretion in a specific way and not by parasympathomimetic effects, led to investigations in several exocrine glands. In salivary glands, amodiaquine did neither stimulate the secretion in all doses investigated nor did it enhance the pilocarpine and acetylcholine induced salivation with any significance and regularity. Also the pancreatic and biliary secretion was neither stimulated by amodiaquine nor was the secretin induced secretion of the pancreas and liver augmented by amodiaquine. Thus the enhancing effect of this drug on the histamine and pentagastrin stimulated gastric secretion was very likely specific for the gastric mucosa and not due to a parasympathomimetic action of the drug. In contrast to the findings in various exocrine glands of the gastrointestinal tract, the arterial hypotension following the i.v. injection of acetylcholine was increased specifically by a preceeding i.v. injection of amodiaquine, whereas the equi-effective actions of histamine, serotonin and bradykinin as well as the hypertension by epinephrine and norepinephrine were not influenced by amodiaquine. This specific effect of the antimalarial drug very probably was not caused by an inhibition of the unspecific choline esterase in the blood. Since in exocrine glands no evidence could be found for a parasympathomimetic action or other modes of action of amodiaquine, it seemed probable that amodiaquine potentiated the histamine and pentagastrin stimulated gastric secretion by an inhibition of histamine methyltransferase in vivo.

Effect of Glucagon on Circulating Gastrin

The effect of glucagon on basal and food-stimulated gastrin release, measured by radioimmunoassay, was studied in normal persons, patients with duodenal ulcer, patients with the Zollinger-Ellison syndrome, and Heidenhain pouch dogs. Intravenous glucagon (30 μg per kg per hr) diminished the basal serum gastrin values and the gastrin response to a standard meal in normal persons, in duodenal ulcer patients, and in dogs. In patients with the Zollinger-Ellison syndrome, glucagon caused an immediate increase in basal serum gastrin concentrations, and did not diminish the gastrin response to a meal. Lowering the glucagon dosage to 0.5 μg per kg per hr did not influence the inhibitory effect on basal values of gastrin or on stimulated gastrin release in normal persons. The effects of glucagon on gastrin are not related to the hyperglycemic effect of glucagon. These effects of glucagon on serum gastrin closely parallel the effects of secretin.

Gastric pepsin secretion by hypothalamo-pituitary-adrenal activation due to intrahypothalamic implantation of adrenaline.

An investigation of gastric secretory response following implantation of a 100 μg dose of epinephrine into various parts of the hypothalamus was undertaken in Heidenhain pouch dogs. The results indicate that the secretion of gastric pepsin increased in animals with implants in the posterior hypothalamus and median eminence. This response was blocked by pituitary stalk section and adrenalectomy. On the other hand, an intravenous injection of 100 μg/kg of epinephrine for control had no effect on gastric pepsin secretion. Thus, it seems reasonable to assume that the locally implanted epinephrine stimulates the hypothalamus, particularly the posterior hypothalamus and/or median eminence, to release adrenocorticotropic hormone, which is responsible for a typical increase in gastric pepsin secretion. This study has demonstrated the presence of a humoral mechanism in the hypothalamo-pituitary-adrenal system with regard to control of gastric secretion.

Pancreatectomy and liver damage: effects on humoral gastric secretion in dogs.

Twelve Heidenhain pouch dogs were examined for pancreatic and hepatic effects on humoral gastric secretion. In three dogs pancreatin and methionine given orally did not change pouch output of acid. Total pancreatectomy was performed in the remaining nine dogs. In three dogs pancreatin and methionine were given immediately after surgery to prevent fatty metamorphosis, and gastric secretion steadily rose to 150% above control levels at 11 weeks. The remaining six dogs were allowed to develop a fatty liver for eight weeks before treatment with pancreatin and methionine was initiated. In three the liver function returned to normal, but there was no alteration of the steady rise in pouch secretion to 376% above control levels at 16 weeks. In the other three dogs the liver function did not return to normal and their average pouch secretion levels rose steadily to 296% above control levels at 16 weeks.

Pepsin secretion by Heidenhain pouches in dogs.

Pepsin secretion by Heidenhain pouches in dogs.

Comparison of the effect of several gastrin-related compounds on acid secretion in dogs

Caerulein, desulfated caerulein, the octapeptide of cholecystokinin, cholecystokinin, and pentagastrin were compared for stimulation of acid secretion from Heidenhain pouches in dogs. Pentagastrin and desulfated caerulein evoked similar maximal rates of secretion. Caerulein and octapeptide of cholecystokinin elicited similar dose-response curves and the maximal secretory rates with these two peptides were less than 50 per cent of that of pentagastrin. Cholecystokinin failed to stimulate pouch secretion over a wide range of doses. When cholecystokinin was added to an infusion of caerulein, acid secretion was inhibited. We interpret these findings as follows: (1) sulfation of tyrosyl in position 7 from the C-terminus in peptides with the active center of gastrin is the essential feature which changes these compounds from full agonists to partial agonists for gastric secretion in dogs; (2) the difference between natural cholecystokinin and the synthetic octapeptide of cholecystokinin for acid secretion probably is due to an enterogastrone other than cholecystokinin or secretin in the cholecystokinin preparation.

Effect of satiety center damage on food intake, blood glucose and gastric secretion in dogs.

Goldthioglucose is capable of damaging the ventromedial hypothalamus (satiety center) and inducing obesity in dogs, similar to the effects reported in mice and rats. Body weight was increased at a rate of 10% or more in 51% of the goldthioglucose-treated dogs during an 8-week period. Daily food intake was also increased, significantly, as high as 20% or more, in 68% of the goldthioglucose-treated dogs. Fasting blood-glucose levels did not show any change in obese animals, but blood glucose utilization increased significantly as compared with control animals. The sensitivity of glucose regulating mechanisms to insulin was enhanced by goldthioglucose treatment. Fasting gastric secretion in Pavlov pouch dogs, increased in volume and acidity, above preinjection levels of goldthioglucose, but this effect was not seen in Heidenhain pouch dogs.

Gastrin and acid studies in the pouch dog. II. Effect of truncal vagotomy on response to food and insulin hypoglycaemia.

Serum gastrin and acid secretion were studied in one Heidenhain and two Pavlov pouch dogs before and after truncal vagotomy. The Heidenhain pouch dog showed an increase in basal serum gastrin and basal acid output following vagotomy, and the secretion of both gastrin and acid was also increased by a meat meal, with prolongation of the duration of response. The Pavlov pouch dogs, although showing a similar rise in both basal and meat-stimulated gastrin after vagotomy, showed a fall in both basal acid output and the peak acid output after meat compared to the levels attained before vagotomy. Insulin hypoglycaemia failed to stimulate either gastrin or acid release post-vagotomy.

胃腸ホルモンに関する研究(第6報<SUP>1)</SUP>)

The anti-secretory and antiulcerogenic activities of a substance, which was a glycopeptide (abbreviated as GGP) and extracted from the mucosa of the third stomach of the finback whale (Balaenoptera physalus L.), were studied in detail. GGP was shown to have a dose-dependent anti-secretory effect on gastric secretion in the Shay's rats with ligated pylorus with intravenous doses of 0.01-2.0 mg/kg. GGP showed a significant suppressing effect on gastric secretion induced by histamine, acetylcholine and tetragastrin in the Schild rats, and also showed the similar effect on histamine- or tetragastrin-induced secretion in the Heidenhain pouch dogs. Not only GGP showed the significant antiulcerogenic activities against the Shay rat ulcers and such experimental peptic ulcers as serotonin, histamine and stress ones, but also is exhibited a definite curative effect on the ulcer induced by acetic acid injection. GGP may induce the anti-secretory effect through direct or indirect inhibition of activity of parietal cells, and the antiulcerogenic effect of GGP may be produced through antisecretory effect.

Effects of cortisone on acid, pepsin, sulfated polysaccharides and glycoprotein secretion by the mucosa of denervated fundic pouches of dogs.

The effects of acute and chronic administration of corticosteroids were studied on the fundic secretion of 10 Heidenhain pouch dogs. Acid, pepsin and chondroitin-4-sulfate secretion is increased durin

Potentiation of Maximal Gastric Acid Response to Pentagastrin by Subthreshold Doses of Methacholine in Heidenhain Pouch Dogs

Varro, V. & Mignon, M. 1970. Potentiation of Maximal Gastric Acid Response to Pentragastrin by Subthreshold Doses of Methacholine in Heidenhain Pouch Dogs. Scand. J. Gastroent. 5, 511-512.Subthreshold doses of a stable choline-ester (methacholine) given together with pentagastrin considerably increased the maximal acid output elicited by the pentagastrin alone in Heidenhain pouch dogs.

Effects of gastric and jejunal juice extracts on gastric acid secretion.

AbstractThe specificity of inhibition of i.v. injected extracts prepared from the gastric antral juice of dogs was studied by comparison with extracts prepared from canine fundic and jejunal pouches. The extracts were prepared by dialysis against water and lyophilization, and injected in doses of 1 mg/kg b.w. into Heidenhain pouch dogs secreting at a steady state from constantly infused histamine. Extracts of antral juice (22 expts. in 5 dogs) were found to inhibit gastric secretion in 17 expts. (average 63.6%), while in 4 expts. there was stimulation of gastric secretion (average 57%). Extracts of fundic juice were tested in 21 expts. in 4 dogs, and showed inhibition in 10 (average 50.4%) and stimulation in 10 expts. (average 54.8%). The extracts obtained from jejunal secretions were tested in 15 expts. on 3 dogs, and showed inhibition of gastric acid secretion in 9 expts. (average 50.6%), while in 4 expts. there was significant stimulation of the secretion (47.7%). Rectal temperature was increased more than 0.5° C in 8 of the experiments with antral juice extracts, in 4 with fundic extracts, and in 7 with jejunal extracts. Inhibition or stimulation was observed in these experiments. It is concluded that dialyzed and lyophilized extracts from gastrointestinal secretions contain substances that either stimulate or inhibit gastric secretion. The inhibitory effect could not be completely explained by pyrogenicity of extracts.

The action of some agents active at autonomic ganglionic sites on the secretory response of the Heidenhain pouch to various stimuli

In Heidenhain pouch dogs, with or without antra, the action of gastrin pentapeptide on acid secretion was augmented progressively by increasing doses of conventional ganglionic blocking agents. Gastrin pentapeptide did not stimulate pepsin secretion, but with pentolinium tartrate pepsin output was augmented. Two muscarinic ganglionic stimulants (AHR 602 and McNa 343) with gastrin pentapeptide or endogenously released gastrin greatly augmented acid and pepsin secretion. A nicotonic ganglionic stimulant (DMPP) did not demonstrate any of these effects. Neither ganglionic blockers nor stimulants of either type augmented histamine or metacholine stimulated gastric acid or pepsin secretion. Neither the blockers nor stimulants influenced gastric acid or pepsin when administered alone. It is concluded that gastrin and gastrin pentapeptide in some respects act to stimulate gastric secretion like muscarinic ganglionic stimulants and in this respect their action differs from that of histamine or cholinergic agents.

Intestinal resection and gastric secretion in dogs with antrectomy.

Previous work from this laboratory 1 established that massive small bowel resection, or intestinal bypass, produces a striking increase in the secretion of acid from Heidenhain pouches in dogs. This observation has been confirmed and extended by similar, though not identical, experiments in other laboratories. 2-7 Although previous attempts have been made to clarify the possible role of the gastric antrum in this postenterectomy hypersecretion, the issue has not been settled. The present study was undertaken to determine if postenterectomy hypersecretion occurs in the absence of the antrum. Method Eight mongrel dogs of both sexes, varying in weight between 12.2 and 18.4 kg were used. Operations were performed aseptically under pentobarbital sodium anesthesia. The animals were maintained on a standard kennel ration and were provided a measured amount of food at the same time each day. Food pans remained in the cages for one hour only and the residual food,

PH-dependence of the mechanism in the duodenal bulb inhibiting gastric acid responses to exogenous gastrin.

AbstractGastric secretion was stimulated by intravenous infusion of gastrin n Pavlov and Heidenhain pouch dogs provided with isolated pouches of the duodenal bulb. Lowering the intrabulbar pH to pH 1.1 –1.3 almost abolished the acid response to a low dose of gastrin, whereas the inhibition of secretory responses to higher doses was less pronounced. Inhibition of secretory responses to a fixed submaximal dose of gastrin did not occur until the bulbar pH was reduced to 2.0–2.5. Secretory responses to threshold doses of gastrin, on the other hand, were significantly inhibited already at pH 3–4. The results question the concept that very low intra‐duodenal pH is required to activate the mechanism by which acid in the duodenum inhibits gastric acid secretion.