Gastric Acid Secretion In Man Research Articles

Acute effects of N-terminal progastrin fragments on gastric acid secretion in man.

We previously identified an N‐terminal fragment of progastrin in human antrum and plasma, where it circulates in high concentrations. In this study, we examined the effects of N‐terminal progastrin fragments on gastric acid secretion by infusion in healthy individuals. Increasing doses of progastrin fragment 1‐35 were infused intravenously during constant gastric acid stimulation by gastrin‐17. In addition, the effects of progastrin fragment 1‐35, fragment 6‐35, and fragment 1‐19 on gastrin‐17 stimulated acid secretion were tested. The gastrin‐17 stimulated acid secretion decreased 30% after administration of a high dose of progastrin fragment 1‐35 (P < 0.05). In extension, a 1‐h infusion of fragment 1‐35 also decreased gastric acid output. In contrast, fragment 6‐35 did not affect acid secretion, and a single infusion of gastrin‐17 alone did not reveal fading of gastric acid output during the time course of the experiments. The results show that N‐terminal fragments of progastrin may acutely affect gastrin‐stimulated gastric acid secretion in vivo. Structure‐function analysis suggests that the N‐terminal pentapeptide of progastrin is required for the effect.

Immunocytochemical identification of low-affinity NTS2 neurotensin receptors in parietal cells of human gastric mucosa

The biological effects of neurotensin (NT) are mediated by two distinct G protein-coupled receptors, NTS(1) and NTS(2). Although it is well established that neurotensin inhibits gastric acid secretion in man, the plasma membrane receptor mediating these effects has not been visualized yet. We developed and characterized a novel antipeptide antibody to the carboxy-terminal region of the human NTS(2) receptor. The cellular and subcellular distribution of NTS(2) receptors was evaluated in various human gastrointestinal tissues. Specificity of the antiserum was demonstrated by (1) detection of a broadband migrating at M(r) 90 000-100 000 in Western blots of membranes from NTS(2)-expressing tissues; (2) cell-surface staining of NTS(2)-transfected cells; (3) translocation of NTS(2) receptor immunostaining after agonist exposure; and (4) abolition of tissue immunostaining by preadsorbtion of the antibody with its immunizing peptide. In the gastrointestinal tract, NTS(2) receptor immunoreactivity was highly abundant in parietal cells of the gastric mucosa, in neuroendocrine cells of the stomach small and large intestine, and in cells of the exocrine pancreas. NTS(2) receptors were clearly located in the plasma membrane and uniformly present on nearly all target cells. The presence of NTS(2) receptors was rarely detected in human tumors. This is the first localization of NTS(2) receptors in human formalin-fixed, paraffin-embedded tissues at the cellular level. The abundant expression of low-affinity NTS(2) receptors on the plasma membrane of human parietal cells provides a morphological substrate for the direct inhibition of gastric acid secretion observed after i.v. administration of neurotensin.

Maximal Gastric Acid Secretion in Man: A Concept That Needs Precision

(1998). Maximal Gastric Acid Secretion in Man: A Concept That Needs Precision. Scandinavian Journal of Gastroenterology: Vol. 33, No. 10, pp. 1009-1015.

Noninvasive assessment of gastric acid secretion in man. Application of electrical impedance tomography (EIT).

Electrical impedance tomography (EIT) is a tubeless technique that generates tomographic images of gastric resistivity. We investigated the application of EIT to measure gastric acid secretion. Nineteen normal subjects underwent a standard intubation test. Basal acid output (BAO) and stimulated acid output (SAO) (millimoles per hour) were measured before and after pentagastrin, respectively. On a different day, EIT was performed before (basal) and after pentagastrin (stimulated). The changes in impedance over time were measured and the area under the curve (AUC) was calculated. Both the tests were repeated in 13 subjects after omeprazole treatment. As in the intubation test, there was the expected increase in AUC value after pentagastrin (basal vs stimulated; 1.2 +/- 2.8 vs 731 +/- 297, P < 0.0001). A significant fall in acid output and AUC following omeprazole pretreatment was observed (without vs with omeprazole; 20.5 +/- 5.7 vs 0.03 +/- 0.06, P < 0.0001 for intubation test and 731 +/- 297 vs 44 +/- 172, P < 0.0001 for EIT). There was a significant correlation between SAO and the delta AUC with (r = 0.65 P < 0.001) or without (r = 0.95, P < 0.001) omeprazole and in all the experiments (r = 0.87, P < 0.001). This study demonstrates the predictable change of gastric impedance and may be useful as a noninvasive test for measuring gastric acid secretion.

Glucagon-Like Peptide-1 7-36 Amide and Peptide YY Have Additive Inhibitory Effect on Gastric Acid Secretion in Man

Background: Glucagon-like peptide-1 7-36 amide (GLP-1) and peptide YY (PYY) are colocalized in the L-cell of the ileal mucosa, and both peptides may function as enterogastrone hormones. However, it is not known whether they interact with regard to the effect on acid secretion. Methods: The effect of intravenous infusion of GLP-1 and PYY, either alone or in combination, on pentagastrin-induced acid secretion in eight healthy volunteers was examined. The peptides were infused at two different rates: 0.25 pmol/kg/min (low rate) and 0.5 pmol/kg/min (high rate). Results: Given alone, GLP-1 and PYY inhibited acid secretion by 26 ± 5% and 18 ± 5% (low rate) and 45 ± 8% and 38 ± 7% (high rate), respectively. Combined infusion resulted in an inhibition of 32 ± 5% (low rate) and 62 ± 7% (high rate). Both infusion rates resulted in GLP-1 and PYY plasma concentrations below or similar to postprandial levels. Conclusion: The present study suggests that the interaction between GLP-1 and PYY in man is of the additive type. The results indicate that GLP-1 and PYY have an important role in the physiologic control of gastric acid secretion.

Cholecystokinin as a physiological regulator of gastric acid secretion in man.

Cholecystokinin as a physiological regulator of gastric acid secretion in man.

Cholecystokinin in the control of gastric acid secretion in man.

This study was designed to determine the role of cholecystokinin in the control gastric acid secretion in men using loxiglumide, a specific cholecystokinin receptor blocker. Three groups of healthy subjects (A, B, and C) were used; group A--for studies with postprandial gastric secretion, group B--for studies with exogenous gastric secretagogues and group C--for 12 hour intragastric pH-metry. Cephalic phase stimulated by modified sham feeding in group A subjects increased gastric acid secretion to about 50% of pentagastrin maximum and the treatment with loxiglumide in a standard dose (20 mumol/kg iv loading dose plus infusion of 20 mumol/kg/h afterwards) failed to affect this secretion. Gastric acid response to a 5% peptone meal instilled intragastrically greatly enhanced gastric acid secretion and plasma gastrin concentration but the addition of loxiglumide in the standard dose resulted in further increase in both gastric acid and plasma gastrin responses to peptone meal. Infusion of caerulein in gradually increasing doses (15-120 pmol/kg/h) and gastrin releasing peptide (25-200 pmol/kg/h) resulted in a dose dependent stimulation of gastric acid secretion reaching about 35% and 25% of maximum attained with pentagastrin. When loxiglumide was added in a standard dose, the acid responses to caerulein and gastrin releasing peptide were further increased two to three fold attaining the peak reaching, respectively, about 100% and 50% of pentagastrin maximum. In group C subjects, 12 hour pH-metry revealed the usual increase in gastric pH after each meal in tests with placebo. Loxiglumide (1200 mg tablets tid, po) resulted in significantly lower pH after each meal and this was accompanied by significantly higher gastrin responses than in placebo tests. We conclude that cholecystokinin released by peptone meal, ordinary meals or gastrin releasing peptide exerts a potent inhibitory influence on gastric acid secretion and gastrin release in men and this inhibition involves subtype A cholecystokinin receptors.

Effects of a CCK-A receptor antagonist on gastric acid secretion in man

Effects of a CCK-A receptor antagonist on gastric acid secretion in man

Cholecystokinin both stimulates and inhibits gastric acid secretion in man

Cholecystokinin both stimulates and inhibits gastric acid secretion in man

CP-66,948: An antisecretory histamine H2-receptor antagonist with mucosal protective properties

CP-66,948 is a histamine H2-receptor antagonist with gastric antisecretory activity and mucosal protective properties. The affinity of CP-66,948 for the guinea pig atria histamine H2-receptor is 15 times greater than that of cimetidine and seven times greater than that of ranitidine. In vivo, the ED50 value for inhibition of gastric acid secretion in pylorus-ligated rats is 2 mg/kg intraduodenally, and in histamine or pentagastrin-stimulated Heidenhain pouch dogs the antisecretory ED50 values are 0.3 mg/kg per os and 1.0 mg/kg per os, respectively. CP-66,948 also inhibits ethanol-induced gastric hemorrhagic lesions in rats following either oral or systemic administration (ED50 values of 12 mg/kg per os and 6 mg/kg subcutaneously). In addition, the mucosal protective activity is independent of prostaglandin synthesis. CP-66,948 inhibits gastric acid secretion in man, and its mucosal protective activity may provide additional benefits in peptic ulcer therapy.

Effects of Pirenzepine and Atropine on Basal Lower Esophageal Pressure and Gastric Acid Secretion in Man: A Placebo-Controlled Randomized Study

Pirenzepine is a tricyclic antimuscarine drug with antisecretory effect on gastric secretion and inhibitory effect on esophageal peristalsis (EP). The effect of pirenzepine in graded doses on basal and pentagastrin-stimulated lower esophageal sphincter pressure (LESP) was studied in 8 volunteers. The effect was compared with the effect of atropine and placebo using a double dummy technique. Intravenously administered pirenzepine and atropine inhibited basal LESP and EP regardless of the employed doses. No difference between atropine and pirenzepine could be demonstrated. The pentagastrin-stimulated LESP was inhibited in patients treated with pirenzepine perorally (50 mg b.i.d.). Basic acid output was significantly reduced by pirenzepine or atropine in contrast to peak acid output. We conclude that muscarinic receptors of type M play a role in the LES function in man.

Glucagon-like peptide-1 (7–36)-NH2: a physiological inhibitor of gastric acid secretion in man

Glucagon-like peptide (GLP)-1 (7-36)-NH2 is a peptide found in the mucosal endocrine cells of the intestine, and plasma levels of GLP-1 (7-36)-NH2 immunoreactivity show a rise after the ingestion of a fat or mixed-component meal. We investigated the effects of physiological infusion of GLP-1 (7-36)-NH2 on a submaximal gastric acid secretion in healthy volunteers at a rate known to mimic the observed postprandial rise in plasma concentrations. Corrected gastric acid output decreased to less than 50% and volume output to 33% of stimulated values. After the infusion, the secretion of gastric acid recovered immediately to preinhibition values. These results suggest a novel role for GLP-1 (7-36)-NH2 as a physiological inhibitor of gastric acid secretion in man.

Inhibition of Gastric Acid Secretion by Jejunal Glucose and Its Relation to Osmolality and Glucose Load

Intrajejunal infusion of hypertonic glucose and hypertonic saline inhibits pentagastrin-stimulated gastric acid secretion in man. This effect is generally ascribed to the hyperosmolality of the solutions. Five volunteers were given 50 g glucose in osmolar concentrations of 2700 mosmol/l and 900 mosmol/l, and five were given 25 g glucose in osmolar concentrations of 2700 mosmol/l and 300 mosmol/l. Control studies with intrajejunal infusion of physiologic saline were performed in all subjects. Median inhibition of gastric acid secretion was 91% after 50 g glucose and 47% after 25 g glucose and was unrelated to the osmolar concentration. These findings suggest that the acid-inhibitory effect of intrajejunally administered glucose is related to the glucose load and not to the osmolar concentration. Plasma responses of intact neurotensin, immunoreactivity, NH2-terminal neurotensin immunoreactivity, enteroglucagon, and gastric inhibitory polypeptide were all related to the amount of glucose given. Glucagon and somatostatin, both of which are potent inhibitors of gastric secretion, were not released by intrajejunally administered glucose.

PHV-42 a novel gastric peptide, stimulates gastric acid secretion in man

PHV-42 a novel gastric peptide, stimulates gastric acid secretion in man

Effect of single and repeated intravenous doses of omeprazole on pentagastrin stimulated gastric acid secretion and pharmacokinetics in man.

Single intravenous doses of 10, 20, 40, and 80 mg and repeated once daily intravenous doses of 10 and 20 mg omeprazole induced a powerful and long lasting inhibition of pentagastrin stimulated gastric acid secretion (PAO) in healthy male volunteers. Single intravenous doses of 10, 20, 40, and 80 mg omeprazole inhibited PAO by 30% (p less than 0.01), 45% (p less than 0.01), 61% (p less than 0.01), and 80% (p less than 0.01), respectively when measured 1.5 h after dose, and by 20% (NS), 27% (NS), 36% (p less than 0.01) and 59% (p less than 0.01), respectively when measured 24 h after dose. Six days after repeated once daily intravenous doses of 10 and 20 mg omeprazole, PAO was inhibited by 63% (p less than 0.01) and 82% (p less than 0.01), respectively when measured 1.5 h after dose, and by 32% (p less than 0.01) and 43% (p less than 0.01), respectively when measured 24 h after dose. The inhibition of PAO by 10 mg administered intravenously as a single bolus injection was comparable with the inhibition by 20 mg as a single oral dose. Repeated once daily administration of 10 mg intravenously and 20 mg orally also resulted in comparable reductions in PAO. The reduction in PAO after repeated once daily oral administration of 20 mg was comparable with the effect of a single intravenous dose of 40 mg. Terminal half lives were short, but significantly (p less than 0.05) prolonged after a single intravenous injection of 80 mg. Repeated once daily intravenous administration of 10 and 20 mg did not result in prolongation of terminal half lives. It is concluded that intravenous administration of omeprazole causes a potent and long acting inhibition of pentagastrin stimulated gastric acid secretion in man. Its potency is augmented after repeated once daily administration.

Effect of nicardipine on gastric acid secretion in man.

The effect of nicardipine on basal and pentagastrin-stimulated gastric acid secretion in normal volunteers was investigated. When compared with saline, an intravenous infusion of nicardipine caused a significant decrease in peak acid output (from 37.8 mmol hour-1 to 28.8 mmol hour-1; P = 0.04) and a small reduction in aspirate volume. Nicardipine had no significant action on basal acid output or volume of aspirate. Proteolytic activity in both the basal and stimulated periods was unaffected by nicardipine as were serum gastrin concentrations. Although calcium channel blocking agents are theoretically antisecretory the present study suggests they are unlikely to have clinically useful therapeutic actions.

Regulation of gastric acid secretion by neurotensin in man. Evidence against a hormonal role.

The present study was designed to evaluate neurotensin as a hormonal regulator of gastric acid secretion in man. After a fat-rich meal, the strongest known stimulus of neurotensin release, plasma neurotensin-like immunoreactivity (NTLI) was elevated from 7.6 +/- 1.9 to 15.5 +/- 2.5 pM. Plasma NTLI was measured with antiserum L170, which requires the biologically active carboxyl-terminal hexapeptide of the neurotensin molecule for recognition and does not crossreact significantly with any known natural catabolite in human plasma. Intravenous infusion of neurotensin at 25 pmol X kg-1 h-1 resulted in a plasma level of 14.7 +/- 2.1 pM, similar to the maximal physiological level observed after the fat-rich meal. Intravenous infusion of neurotensin at 25 pmol X kg-1 h-1 during 2 h, however, failed to significantly inhibit peptone meal-stimulated gastric acid secretion measured by intragastric titration. The 2-h acid output to peptone was 40.8 +/- 6.2 and 41.3 +/- 6.9 mmol during the vehicle and the neurotensin infusion, respectively. Intravenous infusion of neurotensin at 100 or 400 pmol X kg-1 h-1 did not affect acid output, whereas at 1,600 pmol X kg-1 h-1, which resulted in a plasma neurotensin concentration of 725 +/- 80 pM, significantly reduced peptone meal-stimulated gastric acid secretion. The neurotensin-induced inhibition of acid output was independent of the hormone gastrin. The present results provide evidence against a hormonal role for neurotensin in the regulation of meal-stimulated gastric acid secretion in man.

Perspective on the gastric antisecretory effects of misoprostol in man

Misoprostol, a synthetic prostaglandin E 1 analog, has been found to be safe and effective for the treatment of peptic ulcer disease. This brief overview summarizes the gastric antisecretory effects of misoprostol in healthy human subjects using randomized, double-blind, placebo-controlled studies. Misoprostol effectively and dose-dependently inhibited basal gastric acid secretion at single dose of 50, 100 and 200 mcg/subject. Furthermore, misoprostol effectively inhibited meal-, histamine-, coffee- and tetragastrin-stimulated gastric acid secretion. The inhibition of meal-stimulated gastric acid secretion was not a consequence of the reduction of serum gastrin. In addition, misoprostol inhibited noctural gastric acid secretion. In these studies, the titratable acidity, volume, acid output and pepsin activity were inhibited by misoprostol. The extent of the secretory inhibition achieved with the 200 mcg dose of misoprostol was comparable to that of cimetidine administered at a 300 mg dose. The duration of the gastric antisecretory actions was in the order of 3 to 5 hours. We conclude that misoprostol is a potent inhibitor of gastric acid secretion in man.

Do enkephalins participate in vagal activation of gastric acid secretion in man?

The effects of the anticholinergic drug benzilonium bromide and the opiate receptor blocker naloxone, given alone or in combination, on the acid secretory response and on plasma gastrin releasing peptide (GRP) response to sham feeding was tested in eight duodenal ulcer (DU) patients. Naloxone alone had no effect on the acid secretion after sham feeding. Benzilonium reduced basal acid secretion and the acid response to sham feeding but did not abolish the response. The combination of benzilonium and naloxone was not more effective than benzilonium alone. Neither drug, nor the combination had any effect on plasma GRP following sham feeding. It is concluded that enkephalins are unlikely to participate in the acid response to sham feeding in patients with DU.

Misoprostol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of peptic ulcer disease.

Misoprostol is an analogue of prostaglandin E1 and is the first synthetic prostaglandin analogue to be made available for the treatment of peptic ulcer disease. It inhibits gastric acid secretion in man, and there is also some evidence that it limits the extent of gastrointestinal damage induced by ulcerogenic agents in animals and healthy volunteers at doses lower than those required to inhibit acid secretion. This 'cytoprotective' activity has been explained by several mechanisms, but its contribution to the clinical efficacy of misoprostol in healing established ulcers is doubtful since the drug does not appear to be effective in healing peptic ulcers at non-antisecretory dosages. In clinical trials, ulcer healing has been reported in 60 to 85% of patients with duodenal ulcers and 32 to 54% with gastric ulcers receiving misoprostol 200 micrograms 4 times daily for 4 weeks--the recommended dosage. In comparative studies, the percentage of patients with healed ulcers after misoprostol (800 micrograms daily) was not significantly different from that with cimetidine (1200 mg daily), although there was greater pain relief with cimetidine. No study has yet been published concerning the use of misoprostol as maintenance therapy for the prevention of ulcer recurrence, and no long term tolerability data are available. However, in acute ulcer healing studies (2 to 12 weeks in duration) misoprostol has been well tolerated. Diarrhoea was the most commonly reported symptom, and this was only rarely of sufficient severity to interfere with treatment. No evidence of histopathological changes in the gastric mucosa induced by misoprostol have been reported in man. Evidence of uterine stimulant effects in women receiving misoprostol during the first trimester of pregnancy has resulted in the drug being contraindicated during pregnancy. Thus, misoprostol is a new type of antiulcer drug, providing an alternative approach to the therapy of peptic ulcer disease. It has been shown to be effective and well tolerated in the healing of both gastric and duodenal ulcers. Future studies need to identify the specific types of patients likely to obtain most benefit from treatment, in order to define more clearly the place of misoprostol in the treatment of these indications, as well as addressing the possibility of ulcer prevention with lower doses of misoprostol.