Control Of Gastric Secretion Research Articles

Esomeprazole immediate release tablets: Gastric mucosa ex vivo permeation, absorption and antisecretory activity in conscious rats

The aim of this work was to study the esomeprazole activity on the control of gastric secretion after administration of a novel immediate release tablet. The ex vivo permeation of esomeprazole across porcine gastric mucosa from immediate release tablets, containing sodium carbonate or magnesium oxide as alkalinizing agents, was firstly assessed. Pharmacokinetics and pharmacodynamics studies in conscious rats following the administration of immediate release tablets with sodium carbonate, in comparison with delayed-release tablets having the same formula, were also conducted. The results showed an important effect of sodium carbonate and magnesium oxide on the drug release, on the ex vivo trans-mucosal transport and the stability in acid environment. In particular, the presence of sodium carbonate in esomeprazole tablet formulation provided the maximum increase of the drug in vitro transport across the mucosa. Then, the absorption and the antisecretory activity of this proton pump inhibitor orally administered in rats as immediate release tablets containing Na2CO3, was superior but not significantly different compared to delayed-release tablets having the same formula. In the adopted animal model, an activity of esomeprazole from immediate release alkaline formulation was seen also in presence of partial gastric absorption allowing inhibition of proton pumps reached via systemic circulation. This esomeprazole immediate release formulation could be used for the on-demand treatment of acid-related disorders such as gastro-esophageal reflux disease.

Grelin: biological significance and prospects for use in endocrinology

Ghrelin is a peptide consisting of 28 amino acid residues that is secreted in the stomach and to a lesser extent in other organs. It is a stimulant of growth hormone secretion (GHS), promoting the release of GH by activating the so-called GHS-receptors. These receptors are predominantly concentrated in the hypothalamic-pituitary region, but are also found in other tissues, which explains the wide range of effects of GHR, including stimulation of the secretion of GH, prolactin and adrenocorticotropic hormone (ACTH); effects on sleep and behavior, increased appetite and a positive energy balance; diabetic effect on carbohydrate metabolism, control of gastric secretion and peristalsis. In addition, the experiments have repeatedly shown the positive inotropic effect of ghrelin on the heart, vasodilation, and cell proliferation. The wide biological spectrum of action of ghrelin makes it promising to study and apply new knowledge in various fields of medicine: endocrinology, gastroenterology, immunology, oncology and cardiology.

Pattern-dependent vagal control of gastric secretion: The role of histamine mediation

Pattern-dependent vagal control of gastric secretion: The role of histamine mediation

Leptin in the Control of Gastric Secretion and Gut Hormones in Humans Infected with Helicobacter pylori

Background: Leptin, a protein product of obese gene expressed primarily by adipocytes, provides feedback information on the size of energy stores to central OB receptors controlling the food intake, energy expenditure and body weight homeostasis. It has recently been detected in the rat stomach, especially after cholecystokinin (CCK) administration and in human stomach infected with Helicobacter pylori , but its role in gastric secretory functions in humans has not been revealed. This study was designed to determine the involvement of leptin in the control of basal, CCK- and meal-induced gastric H + secretion and plasma gastrin and CCK levels in humans before and after an eradication of H. pylori. Methods: Two groups (A and B) of subjects were used; group A ( n = 7), for comparison of the effects of CCK and leptin on basal gastric H + and plasma hormone (leptin, gastrin and CCK) levels, and group B ( n = 6), for studies on the involvement of leptin in gastric secretory and plasma hormonal responses to vagal stimulation and gastric peptone meal before and after H. pylori eradication. Results: In H. pylori -positive subjects, CCK (12-200 pmol kg -1 h -1 ) given i.v. caused a dose-dependent increase of gastric H + accompanied by a dose-dependent rise in plasma CCK and leptin levels. In contrast, leptin administered i.v. in graded doses (5-80 pmol kg -1 h -1 ) resulted in a gradual inhibition of basal gastric H + secretion and in adose-dependent increment in plasma leptin accompanied by an increase in plasma gastrin without alteration of plasma CCK level. Following eradication of H. pylori by 1- weektriple therapy in group B patients, the infusion of CCK produceda significantly smaller increase in gastric H + secretion and significantly smaller rise in plasma leptin as compared to those before the eradication. Cephalic phase stimulation of gastric secretion induced by modified sham-feeding in group B H. pylori positive subjects increased gastric H + secretion to about 40% of pentagastrin maximum without affecting plasma leptin, gastrin, or CCK level, while gastric peptone meal resulted in the increase in gastric H + response reaching about 70% of pentagastrin maximum accompanied by a marked rise in plasma leptin, gastrin and CCK. The treatment with a standard dose of leptin (20 pmol kg -1 h -1 ) failed to affect sham-feeding-induced gastric H + secretion but reduced significantly the peptone meal-stimulated H + secretion, while raising plasma gastrin in response to this meal. Plasma CCK under basal conditions and after sham-feeding was not affected, but plasma CCK response to gastric meal was significantly reduced by leptin infusion. Eradication of H. pylori did not affect basal or sham-feeding-induced H + secretion but resulted in a significant fall in gastric mealinduced H + and plasma leptin, gastrin and CCK levels. Conclusions: 1) The gastric meal and CCK enhance the release of leptin in H. pylori -positive patients and this leptin is capable of inhibiting basal and meal stimulated gastric H + secretion, while raising plasma gastrin and reducing the plasma CCK levels, and 2) the eradication of H. pylori reduces the postprandial gastric H + and plasma gastrin responses as well as the release of leptin in response to CCK and meal.

Control of gastric secretion.

Control of gastric secretion.

Role of endogenous nitric oxide in the control of gastric acid secretion, blood flow and gastrin release in conscious dogs

Nitric oxide (NO) was shown to mediate gastric hyperemia following secretory stimulation but its role in the control of gastric secretion has not been clarified. Secretory studies were carried out on conscious dogs with chronic gastric fistula, Heidenhain pouch and esophageal fistula, while changes in gastric blood flow were measured in the mucosa of Heidenhain pouuch by laser Doppler flowmetry. Plasma gastrin was determined by radioimmunoassay. Infusion of N G - nitro- l-arginine ( l-NNA) (bolus i.v. injection of 2.5 mg/kg followed by infusion of 0.5 mg/kg/h), a potent inhibitor of nitric oxide synthase, failed to affect basal gastric secretion or plasma gastrin level but suppressed an increase of this secretion induced by sham-feeding, ordinary meat feeding or i.v. infusion of bombesin (0.5 μg/kg/h), pentagastrin (4 μg/kg/h) or histamine (40 μg/kg/h). In tests with feeding and bombesin infusion, l-NNA caused a significant and dose-dependent reduction in plasma gastrin levels. The inhibition by l-NNA of gastric acid secretory response to pentagastrin, histamine or feeding was accompanied by a decline in blood flow. Addition of l-arginine (bolus i.v. dose of 50 mg/kg followed by infusion of 5 mg/kg/h) significantly attenuated the l-NNA induced inhibition of gastric secretion and the reduction in plasma gastrin response as well as in the fall of gastric blood flow. We conclude that endogenous nitric oxide affects the gastric secretion and that this effect is mediated, at least in part, by the changes in the gastrin release and gastric blood flow.

Phaclofen-sensitive GABA-B receptors do not mediate excitatory effects of baclofen on gastric secretion.

The present study investigates the effects of centrally or peripherally administered baclofen on gastric acid secretion from pylorus-ligated rats. The influence of baclofen on basal acid secretion from isolated guinea-pig gastric fundus was also evaluated. At all doses employed, intracerebroventricular baclofen significantly decreased acid secretion, this inhibitory action being antagonized by intracerebroventricular phaclofen. Intravenous baclofen induced both gastric inhibitory and excitatory responses at low and high doses, respectively. Intracerebroventricular phaclofen prevented the inhibitory effect, while neither intracerebroventricular nor intravenous phaclofen modified the stimulant action of parenteral baclofen. Both central and parenteral muscimol did not influence gastric acid secretion. Moreover, baclofen or muscimol were without effect on basal acid secretion from isolated guinea-pig gastric fundus, whereas bethanechol caused a marked and concentration-dependent stimulant action. The present results provide further evidence for the inhibitory role of central phaclofen-sensitive GABA-B receptors in the regulation of acid secretion. In addition they indicate that the hypersecretory effect exerted by parenteral baclofen may depend upon the activation of putative peripheral non-A and phaclofen-insensitive GABA-B receptors. Finally, peripheral GABA receptors do not appear to be significantly involved in the direct control of gastric secretion.

Tachykinins: Effects on gastric secretion and emptying in rats

To test the effects on gastric acid secretion and gastric emptying of non-mammalian (eledoisin, physalaemin, kassinin), mammalian (substance P. neurokinin A, neurokinin B) and synthetic tachykinins (septide, senktide), intracerebroventricular injections of these peptides were given to conscious pylorus-ligated rats (gastric secretory study) or to animals fed with a phenol red meal (gastric emptying study). The tachykinins able to cause central inhibition of acid output were those active on NK2 and NK3 receptors (eledoisin, kassinin, neurokinin A, neurokinin B and senktide). Tachykinins active on NK1 receptors (substance P. physalaemin and septide) were devoid of this activity. The most potent inhibitor was the synthetic NK3 agonist, senktide. All tested natural tachykinins significantly inhibited gastric emptying, the most potent being those active on NK2 receptors. Septide, the synthetic NK1 agonist, had lowest effect and senktide, the synthetic NK3 agonist, was far less active than eledoisin, kassinin and neurokinin A. Thus, specific tachykinin receptors exist in the rat brain that mediate gastric functions: NK3 receptors participate in the control of gastric secretion, while NK2 receptors seem to be involved in the regulation of gastric emptying by activating inhibitory pathways.

Interaction Between Bombesin and Brain Prostaglandins in the Control of Gastric Secretion

Interaction Between Bombesin and Brain Prostaglandins in the Control of Gastric Secretion

Interaction between bombesin and brain prostaglandins in the control of gastric secretion : A. Guglietta, B.J. Irons, and L.H. Lazarus. National Institute of Environmental Health Sciences, LBNT, Research Triangle Park, NC 27709, USA and Institute of Medical Pharmacology III, Universita di Roma, “La Sapienza” 00185 Rome, Italy

Interaction between bombesin and brain prostaglandins in the control of gastric secretion : A. Guglietta, B.J. Irons, and L.H. Lazarus. National Institute of Environmental Health Sciences, LBNT, Research Triangle Park, NC 27709, USA and Institute of Medical Pharmacology III, Universita di Roma, “La Sapienza” 00185 Rome, Italy

Role of neuropeptides in the control of gastric secretion.

Role of neuropeptides in the control of gastric secretion.

Effects of a mast cell stabiliser (FPL 52694) on human gastric secretion.

The effects of a new monochrome mast cell stabilizer (FPL 52694) on gastric secretion have been studied in healthy volunteers. When administered orally for 3 days, FPL 52694 consistently reduced nocturnal and pentagastrin-stimulated secretion of acid by about 50%. Meal-stimulated gastric secretion was not affected by the drug. Inhibition of the gastric secretory response to pentagastrin was not significant when single doses of the drug were administered either into the stomach or the duodenum, but administration of multiple doses resulted in significant inhibition. The drug does not inhibit gastric secretion by injuring the gastric mucosa, since the gastric mucosal barrier to back diffusion of hydrogen ions is not affected. We conclude that this mast cell stabilizer provides an interesting tool for studying aspects of the physiological control of gastric secretion and may have a therapeutic role in peptic ulceration.

Histamine and the gut.

The role of histamine in the gut is reviewed in relation to gastric secretion of acid, pepsin and intrinsic factors. Species-dependence of some of these actions are also discussed. Interactions with other agonists and antagonists in intact and isolated systems provide the basis for models of the role of histamine in control of gastric secretion. This review deals further with histamine H1 and H2 effects on gastrointestinal circulation and musculature including sphincters. The most dramatic application of the development of histamine H2 antagonists has been in the treatment of duodenal ulcer. The use of H2 antagonists in the treatment of duodenal and gastric ulcer, gastrinoma, gastritis, and esophagitis is critically evaluated.

Antramine (Antral Histamine) Antagonizes Somatostatin Inhibition on Endogenous Gastrin-Induced Gastric Secretion

The effects of antramine, an antral histamine (AH), and of synthetic histamine (SH) on acid, pepsin, and gastrin responses to meals alone or in combination with somatostatin were studied in dogs equipped with a Heidenhain pouch. Food-induced acid secretion was potentiated by AH and only slightly increased by SH. Pepsin secretion was increased by AH and decreased by SH. Both AH and SH suppressed the inhibitory activity of somatostatin on food-induced secretion. AH potentiated gastrin response to feeding but decreased it when somatostatin was added to the meal. Since acid secretion was unrelated to gastrin response, it would appear that the secretory effects of AH involve a direct action on secreting cells, itself based on the suppression of somatostatin inhibition. Gastric secretion is probably related to gastrin efficacy on secreting cells, which would result from the antagonistic effects of somatostatin and AH. These data suggest an alternative hypothesis concerning the role of histamine in the control of gastric secretion.

The role of secretin in the control of gastric secretion and emptying in the dog

It is well established that duodenal acidification strongly inhibits gastric acid secretion, gastric emptying rate and gastrin release. These effects are at least partly mediated via hormonal pathways, but it is not known whether they are mediated by the release of one peptide named in the past enterogastrone, or by several peptides acting together. The effects of duodenal acidification on gastric acid secretion and gastrin release can be reproduced by infusion of small doses of secretin and plasma secretin levels increase during duodenal acidification or after a meal. This peptide is thus the most probable candidate as an enterogastrone. It has however never been clearly shown that administration of low doses of secretin do decrease gastric emptying rate as well as acid secretion. Experiments were performed on four dogs with gastric fistulas. A peptone solution was infused into the stomach. The experiments were repeated during infusion of synthetic secretin. Our results indicate that infusion of low doses of secretin reproduce all the effects of duodenal acidification: a significant inhibition of gastric acid secretion, gastrin release and gastric emptying rate.

Nutrient and bowel segment dependency of human intestinal control of gastric secretion.

The gastric secretory effects of protein, fat, and carbohydrate infused at different levels of the small bowel were investigated in seven healthy subjects. Similar caloric loads (53.4 kcal) of protein (essential amino acids), lipid (oleic acid), and carbohydrate (glucose) in isomolar (280 mosmol/l) similar pH (7.4) solutions were infused into 60-cm segments of small bowel (isolated between two occlusive balloons), located distal to the ligament of Treitz (proximal), proximal to the ileocecal valve (distal), and between the two (middle). A submaximal gastric secretory background was provided by continuous intravenous pentagastrin. Protein stimulated acid secretion in the proximal (increase of 8.7 meq/h, representing 84 +/- 5% of control level) and middle (increase of 1.9 meq/h, representing 16 +/- 2% of control level) segments, while it inhibited acid secretion when infused into the distal segment (decrease of 3.7 meq/h, representing 33 +/- 4% of control level). In contrast, both lipid and carbohydrate inhibited acid secretion similarly (33-38% of control level) at all levels of the bowel. The different effects of protein at different levels of the bowel could not be explained by differences in serum gastrin, different degrees of absorption, or different postabsorptive levels of alpha-amino nitrogen. This suggests the presence of hormonal (nongastrin) or neural mechanisms in the proximal bowel to stimulate acid secretion and/or in the distal bowel to inhibit acid secretion. Thus, factors that determine specific nutrient loads to specific segments of bowel can have important physiological effects on gastric acid secretion.

Effects of thyrotrophin-releasing hormone, and methionine-enkephalin on gastric acid and pepsin secretion in the cat.

1 The effect of intravenous administration of thyrotrophin-releasing hormone (TRH) and methionine-enkephalin on gastric acid and pepsin secretions was investigated in conscious cats prepared with chronic gastric fistulae.2 TRH, 20 mug kg(-1) h(-1), did not influence unstimulated gastric acid secretion, nor gastric acid secretion stimulated by submaximal doses of pentagastrin or histamine. Pepsin secretion stimulated by pentagastrin was not influenced by TRH.3 TRH, 20 mug kg(-1) h(-1), significantly reduced the gastric acid and pepsin responses to intravenous infusion of insulin. TRH also significantly reduced the degree of hypoglycaemia seen in response to insulin. TRH, 20 mug kg(-1) h(-1), but not 5 mug kg(-1) h(-1), infused alone resulted in a significant hyperglycaemia.4 It is concluded that the reduction of insulin-stimulated gastric secretion by TRH is not dependent on the hyperglycaemic action of the peptide. The mechanism of action of TRH on insulin-stimulated secretion is discussed with respect to its site of action.5 Methionine-enkephalin or the potent analogue, D-Ala(2), Met-enkephalinamide were without effect on unstimulated gastric secretion, or secretion stimulated by pentagastrin, histamine, and insulin. The opiate receptor antagonist, naloxone, did not significantly alter the gastric acid or pepsin response to insulin.6 It is concluded that there is no evidence that opiates stimulate oxyntic glands directly, nor that the oxyntic cells may possess high affinity binding sites for opiates, nor that endogenous opiates are involved in the control of gastric secretion.

Intestinal segmental control of gastric secretion: Nutrient absorption and hormonal release

Intestinal segmental control of gastric secretion: Nutrient absorption and hormonal release

Paracrine control of gastric secretion in protochordates

Paracrine control of gastric secretion in protochordates

Role of the amygdala and hypothalamus in the control of gastric secretion in human beings.

Stereotaxic surgery on the human being, is an important field of activity at the Institute of Neurology, and surgery for behaviour disorders includes making lesions in the amygdala and in the hypothalamus. During surgery, the concerned deep nuclei of the brain are stimulated to ascertain the situation of the electrodes. This opportunity has been utilized to note the effect of stimulation of the amygdala and the hypothalamus on the production of acid in the stomach.KeywordsGastric SecretionTotal AcidAmygdaloid NucleusPost StimulationStereotaxic SurgeryThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.