Antral Gastrin Release Research Articles

Cyclic Amp and the Release of Antral Gastrin

The isolated, vagally innervated antral pouches in anesthetized dogs were irrigated with 095% acetylcholine chloride (Ach) or a 0.4 M mixture of non-essential amino acids (AA), or distended at 30 cm H2O pressure. In addition,2-deoxy-D-glucose (2-DG) was administered intravenously. Significant increases in antral venous gastrin, caused by gastrin releasers, were associated with a significant rise in cAMP content in the antral mucosa. Acidification of the antrum with simultaneous administration of 2-DG, and acidified AA abolished gastrin release, and significantly reduced mucosal cAMP. Acidified Ach and distension of the antrum with 0.1 N HC1 supressed gastrin levels without significantly changing the mucosal cAMP content. Since the augmented gastrin release was accompanied by an increased mucosal cAMP, the results suggest that cAMP participates in the action of gastrin secretagogues.

Inhibition of vagally induced gastrin release by somatostatin in cats.

The effect of somatostatin was tested on gastrin release induced by electrical vagal stimulation in anaesthetized cats. The antral release of gastrin was determined in the gastric venous outflow by simultaneous recording of gastrin concentration and blood flow. Repeated vagal stimulation at the same frequency and duration caused release of similar amounts of gastrin within the same cat. Infusion of somatostatin, at a rate of 0.5 microng/kg/min, reduced the vagally induced gastrin release to about 40%. Similarly, basal gastrin output was depressed to about 40% of the control values.

IS PEPTIC ULCERATION A HORMONAL DISEASE?

The pathogenesis of peptic ulceration cannot be explained by an abnormal capacity to secrete acid, for ulcers develop in patients who secrete acid normally. Duodenal and gastric ulcers have a common cause. The location of an ulcer in each individual is primarily determined by his capacity to secrete acid at that time. There is a difference between the mechanisms which heal an ulcer and cure a patient of his disease. Procedures that reduce an individual's capacity to secrete acid, heal an ulcer by moving the focus of the ulcerogenic forces to a more proximal site. It is necessary to remove an antral factor if in addition the patient is to be cured of his disease. It is postulated that this antral factor is the gastrin (G17) which is released in abnormal amounts into gastric juice in patients with ulcers and with gastrinomas. The abnormal amount of G17 in gastric juice may be responsible for releasing abnormal amounts of G34 into the circulation from the duodenum and from gastrinomas. The abnormal release of gastrin develops as a result of an impaired response to duodenal acidification manifest in part by an impaired release of secretin. It is postulated that the abnormal stimulation of antral gastrin release may on occasions give rise to antral G-cell hyperplasia, and that the abnormal secretion of gastrin into gastric juice may on occasions give rise to gastrinomas. These abnormalities may cause ulcers by producing an uncontrolled secretion of acid and an abnormal exposure to bile.

The Effect of Antral Distension on Acid Secretion and Plasma Gastrin in Duodenal Ulcer Patients

The effect of antral balloon distension on acid secretion and the plasma gastrin concentration was studied in 8 duodenal ulcer patients. Antral distension significantly increased the acid secretion to about 30% of the peak acid response to pentagastrin without any change in the plasma gastrin concentration. Antral distension and concomitant intragastric neutralization, with the intention of facilitating release of antral gastrin, produced about the same acid response and did not evoke any plasma gastrin increment. The results suggest that the acid response to antral distension in duodenal ulcer patients is evoked without contribution of the gastrin mechanism, and that the acid response is probably mediated via a pyloro-oxyntic reflex. In this respect the duodenal ulcer patient seems to differ from the healthy subject, in whom antral distension produces no acid response, and from the dog, in which release of gastrin as well as pyloro-oxyntic reflex participate in the acid response to antral distension.

Antral gastrin regulation

Experiments have been carried out in humans and animal subjects in an effort to further delineate antral mechanisms of gastrin release. Protein meals and variation of antral pH with buffered saline has been employed. Results show that: 1. 1. Fasting gastrin levels in duodenal ulcer patients and normals are the same. 2. 2. Antral G-cells of duodenal ulcer subjects respond more readily than normals to a protein meal stimulus. 3. 3. Variation in antral pH over the total range of clinical values does not significantly stimulate basal gastrin levels. Significant acid inhibition occurred in normal patients only. 4. 4. G-cell degranulation seems to occur in an alkaline milieu or be blocked by acidity, i.e., more G-cells are seen at an acid pH. 5. 5. The negative feedblock control over antral gastrin release appears to be less efficient in ulcer patients.

Parasympathetic innervation and pancreatic secretion: the role of the gastric antrum.

The role of the antrum on vagally mediated pancreatic secretion was studied in 8 conscious dogs prepared with chronic pancreatic and gastric fistulae. After completion of control studies 6 were subjected to antrectomy and 2 to antroneurolysis (to interrupt submucosal nerve connections); secretory studies were repeated. With the animals secreting in response to secretin(0.03 u per kg-min) or secretin with cholecystokinin (0.05 u per kg-min), the following were administered: 1) insulin 0.2 u/kg; 2) atropine 0.2 and 0.4 mg/kg; 3) insulin after atropine. Insulin hypoglycemia elicited a marked enzyme response. Both antrectomy and antroneurolysis markedly reduced (80%) the enzyme response to insulin hypoglycemia. Atropine 0.2 mg/kg abolished the insulin response and at 0.4 mg/kg inhibited (50%) the enzyme response to cholecystokinin; these effects were unaltered by antrectomy or antroneurolysis. These experiments suggest that the pancreatic enzyme response to insulin hypoglycemia is predominantly mediated through the vagal release of antral gastrin. Furthermore, antrectomy and antroneurolysis do not affect the enzyme response to cholecystokinin nor do they alter the inhibitory effects of atropine. The inhibitio- by atropine suggests that a cholinergic background exerts a permissive effect on CCK-mediated enzyme secretion.

Effect of extragastric and truncal vagotomy on pancreatic secretion in the dog.

In four dogs with chronic pancreatic and gastric fistulas, dose-response studies of pancreatic bicarbonate and protein secretion were done with intravenous infusions of secretin, octapeptide of cholecystokinin (OP-CCK), and 2-deoxyglucose (2-DG). The pancreatic response to a meal and to duodenal perfusion of graded concentrations of HCl, sodium oleate, and tryptophan were also studied. These observations were repeated after division of both the hepatic and celiac vagal branches to produce extragastric vagotomy, and subsequently after transthoracic truncal vagotomy. The responses to secretin, OP-CCK, and to duodenal perfusion of HCl were either unaltered or only slightly decreased by either extragastric or truncal vagotomy. Basal pancreatic secretion and the responses to duodenal perfusion of oleate and tryptophan were markedly depressed by extragastric vagotomy. These findings indicate that tonic vagal activity contributes to basal pancreatic secretion but has little effect on the response of the pancreas to secretin or CCK or on the release of secretin from the intestine. The decreased pancreatic response to intestinally perfused oleate and tryptophan seen after extragastric vagotomy could be caused either by interruption of reflex paths between gut and pancreas or by interference with CCK release. Extragastric vagotomy reduced pancreatic responses to a meal and to 2-DG and subsequent truncal vagotomy caused still further reduction, possibly, at least in part, by depressing release of antral gastrin.

Aberrations in hollander test response after incomplete vagotomy: Compensating effect of antral resection in the dog

Acid secretory and serum gastrin responses to 2-deoxy-D-glucose and insulin were compared in gastric fistula dogs before and after partial vagotomy and pyloroplasty or partial vagotomy and antrectomy. The acid response and serum gastrin curve were basically unaltered by partial vagotomy and pyloroplasty. Based on the data presented, the acid response to insulin hypoglycemia appears to be more dependent on the vagal release of antral gastrin than on direct vagal stimulation of the parietal cell. However, acid response to insulin was profoundly suppressed to only 4 per cent of control levels after partial vagotomy and antrectomy. Although acid response to 2-deoxy-D-glucose was also profoundly depressed to 33 per cent of control levels after partial vagotomy and antrectomy, it was seven times greater than that seen with insulin. Serum gastrin response was abolished after antrectomy to either insulin or 2-deoxy-D-glucose. Finally, the question to which we originally addressed ourselves appears to have been answered and, in terms of response to vagal stimulation, antrectomy appears to compensate for incomplete vagal denervation and may lead to aberrations and misinterpretations, raising serious questions as to the validity of the Hollander test in patients who have undergone distal gastric resection.

Duodenal acidification and antral release of gastrin.

In order to identify the mechanisms responsible for the inhibition of gastric secretion that follows acidification of the duodenum, we studied the effect that perfusion of the duodenum with hydrochloric acid has on the release of antral gastrin that has been stimulated by the local application of acetylcholine chloride. In five dogs, perfusion of the total duodenum significantly decreased peripheral serum gastrin levels. Acid perfusion of either the distal part of the duodenum or the duodenal bulb caused a prompt decrease in gastrin release from the antrum. The findings indicate that the inhibitory effect of duodenal acidification is explained, at least in part, by the inhibition of gastrin release from the antrum.

Antral reactivity: Effect of vagal innervation on antral gastrin release by various stimuli

We have demonstrated that temporary vagal blockade does not decrease gastrin release from an isolated antral pouch when gastrin is stimulated by local factors in the pouch. At the same time this sort of temporary vagal blockade decreases the responsiveness of the Heidenhain pouch to endogenous stimuli from the antral pouch but not to exogenous stimuli. These findings suggest that truncal vagotomy may be more efficient and might achieve a greater degree of gastric secretory reduction than does parietal cell vagotomy. The implications of these findings with regard to parietal cell vagotomy in the treatment of duodenal ulcer are discussed.

Circadian plasma gastrin patterns in feeding and fasting man.

24-hour basal gastric acid collections were obtained from 14 healthy, young adult male volunteers. The hourly secretary pattern, which described a circadian rhythm, was compared to serial plasma gastrin levels in the subjects who underwent 24-hour gastric intubation and aspiration, subjects who ate and exercised freely and subjects who fasted but were unintubated. A circadian rhythm of plasma gastrin levels was observed only in subjects who ate and exercised freely. The results confirm a previous report which concluded that the circadian pattern of gastric acid secretion is unrelated to plasma gastrin levels and supports the belief that the circadian rhythm of plasma gastrin levels is a result of the effects of feeding on antral gastrin release.

The effect of changes in antral pH on the basal release of gastrin.

SummaryGastrin concentrations in the blood draining the gastric antrum were measured by radioimmunoassay during changes in the antral pH. Neutralization of the antrum (raising the basal ambient pH of 3.5-5 to 7 or 8) resulted in a significant increase of antral venous gastrin concentration. Acidification of the antrum significantly lowered, but did not abolish, the basal release of gastrin.These studies demonstrated, by direct measurement of gastrin, the presence of a very sensitive feedback mechanism between antral pH and gastrin release, and that gastrin may be released by simply raising the basal antral pH to 7.

Lower Esophageal Sphincter Pressure Changes After Food Ingestion

The primary function of the lower esophageal sphincter is to prevent reflux of gastric contents into the esophagus. Therefore, changes in lower esophageal sphincter strength after the ingestion of various foods should be of considerable interest. Pressure in the lower esophageal sphincter was recorded continuously in normal subjects using an infused open-tipped system. Test meals consisted of equicaloric quantities of either protein, carbohydrate, or fat in a total volume of 150 cc. After ingestion of ground beef, consistent increases in lower esophageal sphincter pressure were recorded. This effect was eradicated by acidifying the ground meat meal to a pH of 1.2 to 1.3. After glucose ingestion, slight but significant increases in lower esophageal sphincter pressure were found. By contrast, ingestion of a corn oil meal resulted in a decrease in lower esophageal sphincter pressure. Even greater decreases in lower esophageal sphincter were produced by intraduodenal fat. Intraduodenal acidification and exogenous secretin resulted in minimal decreases in sphincter pressure, with much greater decreases in pressure noted after subsequent intraduodenal instillation of fat. The increased pressure after protein and its inhibition by acidification suggest a mechanism through antral gastrin release; the slight rise in pressure after glucose may indicate a minimal gastrin effect, and the pressure decreases following a fat meal most likely are produced by an entero- gastrone other than secretin.

Effect of Truncal Vagotomy on Gastrin Release and Heidenhain Pouch Acid Secretion in Response to Feeding in Dogs

In 4 dogs with gastric fistulae and Heidenhain pouches, serum gastrin responses and Heidenhain pouch acid outputs were measured in response to feeding beef liver, 15 g per kg. Truncal vagotomy was performed and the studies were repeated. Completeness of vagotomy was confirmed by the failure to elicit acid responses from the gastric fistulae after giving 0.5 U of insulin per kg intravenously. Truncal vagotomy altered in opposite directions meal-induced rises in serum gastrin and Heidenhain pouch acid secretion; the rise in serum gastrin decreased by about 50% but Heidenhain pouch acid secretion increased by about 50%. After vagotomy, maximum acid secretion from the Heidenhain pouch in response to pentagastrin increased 2-fold while the response to histamine remained unchanged. The dose of pentagastrin required to elicit a half-maximal response did not change significantly. These studies indicate that the increased Heidenhain pouch acid response to a meal after truncal vagotomy is not due to increased antral gastrin release. Instead, it appears that the pouch is more sensitive to gastrin and perhaps to other stimulants possibly because of the removal of a vagally mediated noncompetitive inhibitor of gastrin.

Effect of Bile Salts on Antral Gastrin Release

In dogs, irrigation of a vagally innervated pouch of the pyloric gland area with solutions containing a mixture of sodium taurocholate and sodium glycocholate has been shown to cause the release of gastrin. Gastrin release in response to the local irrigation of acetylcholine solutions was also potentiated by the simultaneous irrigation with the same mixture of bile salts. Control irrigations of the pyloric gland area with sodium lauryl sulfate, which has a detergent action comparable to that of the bile salt mixture, were without apparent effect on gastrin release, suggesting that the action of the bile salts was not simply a nonspecific effect from local damage to the pyloric gland area mucosa.

The role of the antrum and the vagus nerve in the formation of gastric mucosal histamine.

1. The effects of the vagus nerve and of antral gastrin on the rate of histamine formation (histamine forming capacity, HFC, i.e. histidine decarboxylase activity) in the parietal cell region of the gastric mucosa has been investigated in the following stomach preparations: gastric fistula, denervated Heidenhain pouch, antral resection with gastrojejunostomy, gastrojejunostomy with exclusion of the duodenum and in the intact stomach. The determinations of mucosal HFC were made on fasting rats and on re-fed animals when the effect of feeding was studied.2. In fasting rats with a gastrojejunostomy and the antrum intact the mucosal HFC of the innervated stomach was about 4 times higher than in the corresponding preparation with the antrum resected. In the innervated main stomach the mucosal HFC was about twice as high as in the denervated pouch, indicating that the vagus and endogenous antral gastrin each contribute to maintaining mucosal HFC in the fasting state.3. Acidifying the stomach caused a substantial lowering of the mucosal HFC presumably by inhibiting antral gastrin release, whereas acid in the stomach did not interfere with the elevation of mucosal HFC evoked by injection of gastrin.4. Injection of gastrin elevated mucosal HFC in the innervated main stomach and in the denervated pouch to approximately equal levels. With the dose of gastrin employed there was about a fourfold increase in the HFC of the pouch mucosa.5. In antrectomized rats enhanced vagal influence, evoked by insulin injection or by feeding, raised the mucosal HFC. In rats with the antrum intact and the stomach acidified, insulin injection produced an increased HFC. Thus, a vagal effect on mucosal HFC exists independent of participation of antral gastrin.6. The stable choline esters carbachol and methacholine act directly on the parietal cell without involving mucosal HFC. The vagus nerve and gastrin, however, are assumed to provide secretory stimulation by means of accelerated histamine formation.7. The interrelation between increased histamine formation and hydrochloric acid secretion is discussed.

Comparison of stimulants of antral release of gastrin.

ARTICLESComparison of stimulants of antral release of gastrinAR Cooke, and MI GrossmanAR Cooke, and MI GrossmanPublished Online:01 Aug 1968https://doi.org/10.1152/ajplegacy.1968.215.2.314MoreSectionsPDF (732 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByCombined Upper and Lower Gastrointestinal Endoscopy: A Prospective Study in Alcoholic and Nonalcoholic CirrhosisAlcoholism: Clinical and Experimental Research, Vol. 13, No. 6Alcohol and the Gastrointestinal TractMedical Clinics of North America, Vol. 68, No. 1Morton I. Grossman, M.D. Ph.D.: An Oral HistoryGastroenterology, Vol. 83, No. 1Can endogenous gastrin inhibit canine interdigestive gastric motility?Gastroenterology, Vol. 78, No. 4Effects of taurocholic acid on gastric acid secretion and gastrin releaseGastroenterology, Vol. 78, No. 1EFFECTS OF ALCOHOL ON GASTROINTESTINAL AND PANCREATIC FUNCTION IN ALCOHOLICSGastrin inhibition of the pyloric sphincterThe American Journal of Digestive Diseases, Vol. 21, No. 6Topical calcium and pH effect on gastrin release and parietal cell secretionJournal of Surgical Research, Vol. 18, No. 4The Neuroendocrine Design of the GutGastroenterology, Vol. 67, No. 1The Role of Amino Acids as Stimulants of Antral ReleaseANZ Journal of Surgery, Vol. 44, No. 2Chemical antroneurolysisThe American Journal of Surgery, Vol. 127, No. 1Control of Gastric Emptying by Amino AcidsGastroenterology, Vol. 62, No. 4Ethanol and Gastric FunctionGastroenterology, Vol. 62, No. 3Stimulation of Secretion of Pig Thyrocalcitonin by Gastrin and by Gastrointestinal SecretagoguesRelationship between Antral Acidity and Gastrin Releasing Potency of Chemical StimulantsActa Physiologica Scandinavica, Vol. 83, No. 4On plasma gastrin levels, ph in gastric secretions, and ultrastructural observations of the g cells of the pyloric mucosa under several experimental conditionsGastroenterologia Japonica, Vol. 6, No. 3Effect of food on serum gastrin evaluated by radioimmunoassayGut, Vol. 12, No. 8Effect of antroneurolysis on gastric secretion in dogs with total gastric fistulaBritish Journal of Surgery, Vol. 58, No. 4Reactions to acid in the intestine in health and disease.Gut, Vol. 12, No. 1Immunochemical Measurements of Endogenous Gastrin ReleaseGastroenterology, Vol. 59, No. 4Aspirin, Ethanol and the Stomach15 September 2017 | Australasian Annals of Medicine, Vol. 19, No. 3The simultaneous emptying and absorption of ethanol from the human stomachThe American Journal of Digestive Diseases, Vol. 15, No. 5Potentiation of Acid Output in Man by a Distention StimulusGastroenterology, Vol. 58, No. 5Gastroenterology in Australia, 1949-69.Postgraduate Medical Journal, Vol. 46, No. 534Studies with Antibodies to GastrinGastroenterology, Vol. 58, No. 2Inhibition of Endogenous Gastrin Activity by Antibodies to the Carboxyl-Terminal Tetrapeptide Amide of GastrinGastroenterology, Vol. 58, No. 2Gastric and Pancreatic Secretion in Response to Gastric Distention in DogsGastroenterology, Vol. 57, No. 3THE PYLORIC ANTRUM AS A REGULATOR OF GASTROINTESTINAL SECRETIONS1 May 1969 | Medical Journal of Australia, Vol. 1, No. 18 More from this issue > Volume 215Issue 2August 1968Pages 314-317 Copyright & PermissionsCopyright © 1968 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1968.215.2.314PubMed5665161History Published online 1 August 1968 Published in print 1 August 1968 Metrics

Gastric Hypersecretion following Intraduodenal Injection of Pancreatic Juice or Non-absorbable Antacid

WE have carried out a series of experiments intended to explain the increase in gastric secretion found in the dog when the pancreatic ducts are ligated or when all pancreatic juice is diverted to the outside. This hypersecretion was first demonstrated by Greenlee1, who transplanted a segment of duodenum containing the principal pancreatic duct into a subcutaneous position where it could drain to the outside, and then anastomosed the residual duodenum end-to-end to re-establish intestinal continuity. This gastric hypersecretion was also found by McIlrath2 when the principal pancreatic ducts were ligated. Some authors feel that this phenomenon could be explained by gastrin released from the pancreas, but we think that obstruction to the duodenum with consequent release of duodenal and antral gastrin is responsible for the increased gastric secretion observed.

THE ROLE OF INTRINSIC NEURAL PLEXUSES IN RELEASE OF GASTRIC ANTRAL GASTRIN.

THE EXISTENCE of a gastric hormone which stimulated acid secretion was first postulated by Edkins 1 in 1906. Some 42 years ago Grossman 2 clearly demonstrated its existence as liberated by various secretagogues. More recently, elaborate experiments by Oberhelman, et al 3 and by Pe Thein and Schofield 4 have shown that vagal stimulation can liberate gastrin.* The former suggested that increased peristaltic activity resulting from insulin hypoglycemic vagal stimulation or from the ingestion of food was the basic mechanism for the release of gastrin. But, because of the disassociation of motility and vagal gastrin release noted by Pe Thein and Schofield, 4 it has been postulated that there are two types of cholinergic fibers in the gastric antrum; one that mediates gastrin release and one that mediates motility. The following study was designed to study further the intimate mechanism for the vagal release of gastrin. Method In each of

VAGAL RELEASE OF GASTRIN IN CATS FOLLOWING RESERPINE.

AbstractReserpine treatment of nonanesthetized cats has previously been shown to sensitize the HCl‐secreting cells to injected gastrin, probably by a centrally induced enhancement of vagal tone. Indications were obtained also of an interference with the gastrin mechanism. Since vagal impulses are considered to be able to release gastrin, the effect of reserpine on the gastrin activity of the antral and duodenal mucosa has been investigated. Gastrin was extracted from the mucosae of reserpine‐injected and untreated cats and the secretory activity of the preparations determined on nonanesthetized gastric nstula cats. An intramuscular injection of 0.10 mg of reserpine per kg b. w. reduced the gastrin activity of the antral mucosa by about 60 per cent in 24 hrs. Neither a 20‐fold increase in dose nor repetition of the injection of 0.10 mg per kg every 24 hrs for 2 or 4 days produced any further reduction and the gastrin activity returned to normal level despite repeated injections for 8 days. An intravenous infusion of 0.03 mg of reserpine per kg, which produces gastric hypersecretion of acid for several hours, caused no significant alteration in the gastrin activity of the antral mucosa. The gastrin activity of the duodenal mucosa amounted to about one‐tenth the activity of the antral mucosa and was reduced by 0.10 mg of reserpine i. m. daily for 2 or 4 days. Bilateral vagotomy did not alter the gastrin activity of either the antral or doudenal mucosa nor did the i. m. injection of 0.10 mg of reserpine per kg daily for 2 days in vagotomized cats. It is suggested that reserpine causes release of antral and duodenal gastrin by central vagal activation. The significance of gastrin release as a mechanism by which reserpine activates the HCl‐secreting cells is discussed.