Effect of two antiserotoninergic drugs,methysergide and metergoline,on gastric acid secretion and gastrin release in healthy man

Summary The effects of acute oral administration of the antiserotoninergic drugs methysergide (3 mg) and metergoline (4 mg) on basal, submaximal (0.6 µg/kg i. m.) and maximal (6 µg/kg) pentagastrinstimulated gastric acid secretion, as well as on basal and food-induced gastrin release, have been evaluated in healthy volunteers. Methysergide significantly increased basal and submaximal pentagastrin-stimulated gastric acid secretion, and metergoline significantly inhibited gastric acidity in all experiments. Basal and stimulated serum gastrin concentrations were not modified by either drug. The effect of methysergide on gastric acid secretion was opposed to that of serotonin and was probably dependent on its antiserotoninergic action, but the decrease in gastric acidity caused by metergoline is not easily explained. Although the effect is similar to that of a dopamine infusion, it does not depend on dopamine receptor stimulation, since it was not influenced by pretreatment with metoclopramide. It is suggested that it might be due to the weak anticholinergic and/or antihistaminic properties of metergoline.     

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.     

Three months of octreotide treatment decreases gastric acid secretion and argyrophil cell density in patients with Zollinger-Ellison syndrome and antral G-cell hyperfunction

Methods: The effects of three months of treatment with octreotide on gastric acid hypersecretion induced by hypergastrinaemia were investigated in patients with Zollinger-Ellison syndrome (n= 5) or antral G-cell hyperfunction (n= 4). Gastric acid secretion, fasting plasma gastrin concentrations and clinical findings were examined, and a morphometrical analysis of oxyntic endocrine cells was performed. Results: Administration of octreotide 100 meg b.d. subcutaneously significantly decreased the volume density of argyrophil cells (P < 0.05) as well as basal and pentagastrin-stimulated acid secretion (P < 0.05). Although partial or complete loss of inhibition was found in most patients after 3 months, gastrin levels were decreased during the first 2 months of treatment (P < 0.05). Fundic D-cells were not affected by treatment. Positive correlations were observed between volume density of argyrophil cells and basal acid output (r= 0.65); plasma gastrin and basal acid output (r= 0.74); plasma gastrin concentrations and volume density of argyrophil cells (r= 0.80). Conclusion: These results support the important role of the enterochromamn-like cell in maintaining acid secretion, and indicate a specific role for octreotide in the therapy of gastric acid hypersecretion associated with hypergastrinaemic diseases.     

Duration of effect of lansoprazole on gastric pH and acid secretion in normal male volunteers

AIM: A double-blind, placebo-controlled study to assess the duration of effect of lansoprazole 30 mg o.m. on intragastric pH, acid secretion, gastrin levels, the potential for rebound acidity, and the relationship between gastric acid and drug pharmacokinetic parameters. METHODS: Sixteen subjects were treated with lansoprazole 30 mg daily or placebo for 14 days, followed by a 7-day post-dosing period and a post-study evaluation on day 28. Ambulatory 24-h pH was recorded and pentagastrin-stimulated acid secretion measured. Plasma kinetics of lansoprazole were determined. RESULTS: Mean intragastric pH in the lansoprazole group increased significantly (P < 0.05) from baseline to day 14 compared to placebo. After cessation of treatment, secretory activity, as measured by intragastric pH, basal acid output and stimulated acid output, returned to baseline in 2 to 4 days without any overshoot, indicating the absence of acid rebound. Lansoprazole's terminal disposition half-life was 1.11 h. Mean pH and serum gastrin returned to baseline with half-lives of 22 and 19 h, respectively. CONCLUSIONS: Lansoprazole 30 mg daily significantly increases mean intragastric pH without producing acid rebound. Regeneration of acid production depends primarily on de novo synthesis of the acid pump.     

Effect of netazepide,a gastrin/CCK2 receptor antagonist,on gastric acid secretion and rabeprazoleinduced hypergastrinaemia in healthy subjects

Aims

To compare gastric acid suppression by netazepide, a gastrin/CCK₂ receptor antagonist, with that by a proton pump inhibitor (PPI), and to determine if netazepide can prevent the trophic effects of PPI-induced hypergastrinaemia.

Methods

Thirty healthy subjects completed a double-blind, randomized, parallel group trial of oral netazepide and rabeprazole, alone and combined, once daily for 6 weeks. Primary end points were: basal and pentagastrin-stimulated gastric acid and 24 h circulating gastrin and chromogranin A (CgA) at baseline, start and end of treatment, gastric biopsies at baseline and end of treatment and basal and pentagastrin-stimulated gastric acid and dyspepsia questionnaire after treatment withdrawal.

Results

All treatments similarly inhibited pentagastrin-stimulated gastric acid secretion. All treatments increased serum gastrin, but the combination and rabeprazole did so more than netazepide alone. The combination also reduced basal acid secretion.Rabeprazole increased plasma CgA, whereas netazepide and the combination reduced it. None of the biopsies showed enterochromaffin-like (ECL) cell hyperplasia. Withdrawal of treatments led neither to rebound hyperacidity nor dyspepsia.

Conclusions

Netazepide suppressed pentagastrin-stimulated gastric acid secretion as effectively as did rabeprazole. The reduction in basal acid secretion and greater increase in serum gastrin by the combination is consistent with more effective acid suppression. Despite our failure to show rabeprazole-induced ECL cell hyperplasia and rebound hyperacidity, the increase in plasma CgA after rabeprazole is consistent with a trophic effect on ECL cells, which netazepide prevented. Thus, netazepide is a potential treatment for the trophic effects of hypergastrinaemia and, with or without a PPI, is a potential treatment for acid-related conditions.     

Effect of nifedipine on gastric acid secretion and gastrin release in healthy man

Summary Nifedipine, a calcium-channel antagonist widely used in cardiovascular disease, has recently been reported to be effective in the treatment of oesophageal motor disorders. The effect of a single therapeutic dose of nifedipine (20 mg p.o.) has been evaluated on basal and submaximal pentagastrin-stimulated gastric secretion and meal-stimulated gastrin release in healthy man. In comparison with placebo, nifedipine significantly decreased both basal and stimulated gastric acidity and juice volume, whereas only a slight but insignificant reduction in meal-stimulated gastrin levels was observed after drug administration. The results are in agreement with previous reports that calcium is involved in stimulus-secretion coupling in the human parietal cell. They do not confirm the effect of calcium on G-cells, although it is likely that doses of nifedipine higher than those commonly used might be effective in the reduction of gastrin secretion.     

Cure of Helicobacter pylori infection in atrophic body gastritis patients does not improve mucosal atrophy but reduces hypergastrinemia and its related effects on body ECL-cell hyperplasia

BACKGROUND: The effects of H. pylori eradication on atrophic body gastritis are controversial. AIM: To investigate the effect of triple therapy on atrophic body gastritis in H. pylori-positive patients and its effect on morpho-functional gastric parameters. METHODS: Thirty-five consecutive atrophic body gastritis patients with histological/serological evidence of H. pylori infection were treated. Before and 6 and 12 months after H. pylori eradication the patients were evaluated for fasting gastrinemia and pepsinogen I, basal and peak acid output, and detailed histological assessment including the ECL cell proliferative patterns. RESULTS: Six months after treatment, 25 out of 32 patients were cured (78%). Cure of infection was associated with improvement in both basal (basal acid output mean 0.23 +/- 0.14 mmol/h vs. 1.75 +/- 0.7 mmol/h, P < 0.005) and stimulated acid secretion (peak acid output mean 3.0 +/- 1.06 mmol/h vs. 16.6 +/- 4.1 mmol/h, P=0.0017) as well as with reduction in hypergastrinemia (mean gastrin levels 444.1 +/- 110.7 pg/mL vs. 85.3. +/- 28 pg/mL; P < 0.005). In contrast, the eradication had no effect on body corporal atrophy and intestinal metaplasia, or pepsinogen I levels (mean 16.6 +/- 2.9 ng/mL vs. 14.2 +/- 2.1 ng/mL, N.S.). These results were confirmed at 12 months after eradication. A statistical inverse correlation was obtained (r=-0.3635, P < 0.05) between the corporal chronic infiltrate score and peak acid output values. A total of 53% of atrophic body gastritis patients showed a regression in severity of body ECL cell hyperplastic change. CONCLUSION: Cure of H. pylori infection in patients with atrophic gastritis reverses some adverse effects on gastric function and ECL cell hyperplasia. H. pylori infection may be cured in atrophic body gastritis patients with partial reversion of its negative consequences on acid secretion and body ECL cell hyperplasia.     

Inhibitory effect of isoprenaline on gastric acid secretion in the rat. The role of endogenous histamine

In dogs beta-adrenoreceptor agonists inhibit gastric acid secretion stimulated by exogenous gastrin to a much greater extent than acid secretion stimulated by exogenous histamine. One possible explanation for this observation is that endogenous histamine is important in gastrin-mediated acid secretion and that isoprenaline and related beta-adrenoreceptor agonists block gastric mucosal histamine release. This possibility was tested in the present study in gastric lumen-perfused anaesthetized rats. Intravenous infusion of isoprenaline (12 microgram kg-1 h-1) inhibited maximal, pentagastrin-stimulated acid output by 50-70% (P less than 0.01), but had no significant inhibitory effect on the maximal acid secretory response to histamine. In contrast to its inhibitory effect on gastrin-stimulated acid output, isoproterenol had no effect on gastric histamine output during pentagastrin infusion. We conclude that isoprenaline selectively inhibits gastrin-stimulated acid secretion in the rat, as in the dog, and by a mechanism other than inhibiting gastric histamine release.     

Effect of sulpiride isomers on gastric acid and gastrin secretion in healthy man

The effects of the antidopaminergic drug sulpiride on gastric acid secretion and gastrin release have been evaluated in 42 healthy individuals. Basal and submaximal pentagastrin (0.5 micrograms/kg-h)-stimulated gastric acid secretion, as well as basal and meal-induced gastrin secretion, were studied after acute intramuscular administration of racemic sulpiride (100 mg) and its L-(50 mg) D-(50 mg) isomers. Racemic and L-sulpiride significantly decreased stimulated serum gastrin concentration, but they did not affect fasting serum gastrin or basal and stimulated gastric acidity. D-sulpiride significantly decreased gastric acid secretion, without affecting serum gastrin levels. While the effects of racemic and L-sulpiride are analogous to those of other antidopaminergic drugs, D-sulpiride mimics the action of dopamine, at least at gastric level. These data support the hypothesis that the D-isomer may possess agonist-antagonist activity at dopamine receptors. Since racemic sulpiride has been used with conflicting results in the therapy of patients with peptic ulcer, in the light of the present results it would be of interest to study separately the efficiency of the D- and L-isomers of the drug in healing peptic ulcer.     

Effect of enprostil on basal and meal-stimulated gastric acid and pepsin secretion, serum gastrin and gastric emptying in healthy persons

Ten healthy volunteers took part in a double-blind, randomized, cross-over study of the effect of single doses of enprostil (70 micrograms) and placebo on basal and meal-stimulated gastric acid, pepsin secretion and serum gastrin. Meal-stimulation was induced by modified sham feeding combined with repeated gastric instillation and withdrawal of meat soup. When studied between 1 and 2.5 hours after oral administration of the drug, enprostil decreased basal acid output by 92% (P less than 0.001) and stimulated acid output by 70% (P less than 0.001). Basal and stimulated volumes of gastric juice were decreased by 50% (P less than 0.02) and 35% (P less than 0.002), respectively. Enprostil decreased stimulated pepsin output by 34% (P less than 0.05), but had no effect on the concentration of pepsin. Neither basal nor stimulated serum gastrin concentrations were affected by enprostil. Percent recovery of the meal was measured by an unabsorbable marker, polyethylene glycol, instilled into the stomach mixed with the soup. Polyethylene glycol recovery decreased from 89% with placebo to 67% with enprostil (P less than 0.01), indicating an enhanced gastric emptying rate with enprostil.     

A comparative study on gastric emptying and secretory status in the early postoperative period after truncal vagotomy with two pyloroplasty variants performed for peptic ulcer disease. II. Heineke-Mikulicz pyloroplasty and comparison with the cassimally routine

In 14 peptic ulcer patients undergoing truncal vagotomy with Heineke-Mikulicz pyloroplasty (VTP-HM), gastric emptying of a radiolabeled solid meal, gastric acid secretion and gastrin release was examined within a median of 14 days (range; 10 to 63 days) following the operation, and compared with the results obtained in 14 patients subjected to vagotomy and Cassimally pyloroplasty (VTP-Cas). VTP-HM markedly disturbed gastric emptying in 10 out of 14 patients (71%), four of which (28%) had extremely rapid, and six (43%) exhibited abnormally delayed gastric emptying. Due to a wide inter-subject variability, no significant differences between VTP-HM and VTP-Cas were found for any of the gastric emptying parameters considered. The basal acid output was significantly lower after VTP-Cas than VTP-HM: 2.4 +/- 0.8 vs 5.8 +/- 1.0mmol.h-1, (p less than 0.02). The difference in pentagastrin-stimulated gastric acid secretion: 9.4 +/- 1.4 vs 12.0 +/- 1.8 mmol.h-1 for VTP-Cas vs VTP-HM, respectively, was not statistically significant. Higher fasting serum gastrin concentration (102.0 +/- 21.1 vs 63.3 +/- 8.3 ng.l-1), and greater postprandial gastrin release (AUC0-120: 16690 +/- 2648 vs 10654 +/- 1283 ng.l-1 min) were observed after VTP-HM than after VTP-Cas. The respective differences did not, however, reach the level of statistical significance, the possible clinical relevance of the differences between the two pyloroplasty procedures with respect to their effect on gastric evacuatory and secretory functions is discussed.     

Effect of mifentidine on peptone meal-stimulated gastric acid secretion and plasma gastrin levels in duodenal ulcer patients

Mifentidine is a new H2-receptor antagonist with distinct characteristics of potency and long plasma half-life. The aim of this study was to evaluate the effects of mifentidine on peptone meal-stimulated gastric acid secretion. Nine duodenal ulcer patients in remission were enrolled in the study and given in double-blind and at random, on two different occasions, a single tablet of 10 or 20 mg mifentidine or placebo according to an incomplete balanced block design. Ninety min after ingestion of the drug, basal gastric secretion was collected for 30 min and volume, pH and acid output determined. Thereafter, the acid output following peptone meal-stimulation was measured for 2 h by a modified version of the intragastric titration method of Thompson and Swierczek. Plasma samples were collected for gastrin and mifentidine determinations. Basal acid output was strongly inhibited by both the low dose (-78%) and the high dose (-98%) (p less than 0.01). The peptone meal-stimulated acid output was reduced in a dose-dependent manner (-45% by 10 mg and -90% by 20 mg). The drug did not affect the fasting serum gastrin levels but increased, although not significantly, the gastrin response to food. The log of the area under the mifentidine plasma levels correlated linearly with total acid output (p less than 0.01). The results of this study indicate that mifentidine dose-dependently suppresses basal acid secretion and reduces peptone-stimulated gastric acid secretion in duodenal ulcer patients.     

Role of somatostatin receptors on gastric acid secretion in wild-type and somatostatin receptor type 2 knockout mice

Somatostatin, probably acting through somatostatin type 2 receptors (SSTR2), is the main inhibitor of gastric acid secretion. We characterized gastric acid secretion in SSTR2 knockout mice, and used preferential somatostatin receptor agonists to assess the relative role of SSTR1, 2, 3, 4, and 5 on gastric acid secretion. Basal gastric acid secretion and the secretory response to a meal were similar in conscious wild-type and knockout mice. However, under urethane anesthesia, which releases endogenous somatostatin, SSTR2 knockout mice had a basal secretion 11–15-fold higher than wild-type animals (mol/10 min:1.40±0.09 vs. 0.10±0.01, p<0.05). Gastrin immunoneutralization or H₂ receptors blockade (cimetidine), but not cholinergic blockade (atropine), reduced the high basal secretion in SSTR2 knockout mice. In SSTR2 knockout mice, gastrin and histamine stimulated acid secretion with similar efficacy, while in wild-type mice histamine was more effective than gastrin. SSTR2 knockout mice showed also a hypersecretory response to pylorus ligation compared with wild-type animals. In wild-type mice, somatostatin-14, SMS 201-995, and the SSTR2-preferential agonist, DC 32–87, inhibited gastrin-stimulated acid secretion with an order of potency SMS 201–995>DC 32–87>somatostatin-14. Preferential agonists for the SSTR1, 3, 4, and 5 were devoid of any effect. None of the compounds tested affected the high basal secretion observed under urethane anesthesia in SSTR2 knockout mice. These results show that gastric antisecretory effects of peripheral somatostatin are mediated solely through SSTR2. In the absence of functional SSTR2 other somatostatin receptors do not compensate for the lack somatostatin-SSTR2-mediated inhibition. Basal acid secretion and the response to a meal are normal in conscious SSTR2 knockout mice, suggesting the presence of somatostatin-independent mechanisms that compensate for the lack of somatostatin-SSTR2-mediated inhibitory responses.     

A comparative study on gastric emptying and secretory status in the early postoperative period after truncal vagotomy with two pyloroplasty variants performed for peptic ulcer disease. I. Cassimally pyloroplasty

Gastric emptying (GE) of a radiolabeled solid meal, gastric acid secretion and gastrin release were examined within a median of 15.5 days (range: 9 to 66) after surgery in 14 peptic ulcer patients subjected to truncal vagotomy with Cassimally pyloroplasty (VTP-Cas). A significant delay in GE was observed after VTP-Cas; the median slope of GE curves, K, decreased from 14.65 (range: 2.56 to 21.86) before to 4.05 (range: 0 to 11.67) min-1.10-3 after the operation (p less than 0.002). The postoperative GE was significantly slower than in a group of 41 healthy controls (median K = 9.09, range: 3.72 to 28.66 min-1.10(-3), p less than 0.01 vs the VTP-Cas-operated patients), and was characterized by a biphasic pattern with a slowed second phase. VTP-Cas resulted in a reduction of the basal acid secretion by an average of 87% (from 9.5 +/- 3.4 to 1.2 +/- 0.2 mmol.h-1, p less than 0.05), and the pentagastrin-stimulated acid output by 72% (from 30.8 +/- 7.2 to 8.6 +/- 1.6 mmol.h-1, p less than 0.05). The fasting serum gastrin concentration remained unchanged after VTP-Cas (68.2 +/- 10.8 pre- vs 67.3 +/- 9.4 ng.1-1 post-operatively), whereas a slight and statistically insignificant increase in the meal-induced gastrin release was found following the VTP-Cas-AUC0-120: 10002 +/- 1298 pre- vs 11234 +/- 1422 ng.1-1 min postoperatively.     

An alprostadil analogue and human gastric secretion. A double-blind placebo-controlled study of the effects of a tablet and lyovial formulation

The effects of single doses of 800 micrograms and 1200 micrograms of the new alprostadil analogue (prostaglandin E1 16-methyl-16-methoxy derivative) MDL 646, presented as tablet and lyovial formulations, on basal and pentagastrin-stimulated gastric acid secretion, were studied in 10 normal male volunteers using a randomised, double-blind placebo-controlled cross-over design. Compared to placebo, both doses of MDL 646 significantly decreased acid output during the basal and pentagastrin-stimulated periods. No difference between the tablet and lyovial formulations was found. Total basal output (tablet and lyovial data pooled) was reduced by 58% and 68% following 800 micrograms and 1200 micrograms MDL 646, respectively. Stimulated output was reduced to a lesser degree (15% and 27%). Inhibition of the stimulated acid secretion was observed up to 1.5 to 1.75 h after drug administration. Tolerance was good with only one subject reporting nocturnal abdominal pain following each dose of the drug and placebo.     

Comparison of lansoprazole with omeprazole on 24-hour pH, acid secretion and serum gastrin in healthy volunteers

Background: Lansoprazole and omeprazole are proton pump inhibitors which both strongly inhibit acid secretion, resulting in a significant increase in serum gastrin levels. However, no direct comparison of recommended doses (20 mg for omeprazole and 30 mg for lansoprazole) has been reported so far. Our aims were to compare the effects of omeprazole 20 mg/day and lansoprazole 30 mg/day on intragastric acidity and serum gastrin concentration in 12 healthy volunteers. Methods: The study was double-blind, randomized and placebo-controlled with a cross-over design. On the seventh day of each period, 24-hour intragastric pH was measured using a combined glass electrode placed in the proximal stomach. The last morning dose of each regimen was taken at the end of 24-hour pH monitoring; acid output and serum gastrin concentrations were then studied in the fasting state and after stimulation with pentagastrin (maximal acid output) and a meal (post-prandial gastrin response). Results: Compared to placebo, both drug regimens induced a sustained increase of 24-hour intragastric pH and significantly decreased basal and pentagastrin-stimulated acid secretion. Lansoprazole 30 mg was slightly more effective than omeprazole 20 mg in terms of time spent above pH 3 (P < 0.05). Accordingly post-prandial gastrin concentrations rose slightly more after lansoprazole than after omeprazole. All other differences were insignificant. Conclusions: Both lansoprazole 30 mg and omeprazole 20 mg induce potent and long-lasting acid inhibition, with few minor differences when the two proton pump inhibitors are used at standard doses.     

Intravenous and oral lansoprazole are equivalent in suppressing stimulated acid output in patient volunteers with erosive oesophagitis

BACKGROUND: Some patients requiring acid suppression may be unable to take oral medications. AIM: To compare the gastric acid inhibition effects of lansoprazole 30 mg administered either intravenous or orally in erosive oesophagitis patients. METHODS: The study included 87 Helicobacter pylori-negative patients with erosive oesophagitis. Each patient received 7 days of lansoprazole 30 mg orally prior to being randomized in a 3:1 fashion to intravenously lansoprazole 30 mg or intravenously placebo for 7 days. Basal acid output and pentagastrin-stimulated acid output were measured on days 8, 9 and 15. RESULTS: Median pentagastrin-stimulated acid output was 7.2 mmol/h after 7 days of oral lansoprazole. The median pentagastrin-stimulated acid output increased to 7.6 mmol/h after 7 days of intravenous lansoprazole compared with 26.9 mmol/h after intravenous placebo (P < 0.001). CONCLUSIONS: Lansoprazole 30 mg administered intravenous was equivalent to the 30 mg oral capsule in gastric acid suppression. Intravenous proton pump inhibitor therapy represents an important treatment option for those with acid-related diseases who are unable to take oral medications.     

In vitro inhibition of gastric acid secretion by vasopressin

Interpretation of studies designed to investigate the inhibitory action of vasopressin on gastric acid secretion has proven difficult, as the in vivo models are potentially susceptible to both direct (e.g. mucosal effects) and indirect effects (e.g. changes in mucosal blood flow). In the present series of experiments we studied vasopressin inhibition of both basal and histamine-stimulated acid secretion in rat isolated gastric mucosa, a preparation which is independent of blood flow. Basal and histamine-stimulated levels of acid secretion were 2.32 +/- 0.10 (mean +/- S.E.) and 4.36 +/- 0.41 mu eqH+/h per cm2. Vasopressin inhibited both basal and histamine-stimulated acid secretion; the effect, which was maximal at 15 min post-dosing, was blocked by the specific V1 antagonist d(CH2)5Tyr(Me) AVP. No effect on acid secretion was evident with either the potent V2 agonist, dDAVP, or oxytocin, a neurohypophyseal hormone which can also affect water retention and blood pressure. These studies demonstrate that vasopressin can specifically inhibit mucosal acid secretion; the inhibitory effect is most likely mediated via a V1 vasopressin receptor subtype on the gastric mucosa.     

Effect of high dose omeprazole on gastric pepsin secretion and serum pepsinogen levels in man

Summary To investigate the effect of omeprazole on serum and urinary pepsinogens and on gastric pepsin, 8 healthy male volunteers were studied before and after 9 days of treatment with omeprazole 60 mg/day p.o. Fasting serum samples and 24 h urine specimens were obtained, and gastric contents were aspirated at 15-min intervals, 4 prior to and 6 during pentagastrin 1.5 µg·kg^–1·h^–1 i.v. during intra-gastric perfusion with NaCl 0.9% and phenol red 3 mg·ml^–1 as an inert recovery marker.Basal and pentagastrin-stimulated volume and acid secretion were significantly decreased. The basal and pentagastrin stimulated pepsin output remained unchanged but pepsin concentration in gastric secretion was increased. Administration of omeprazole resulted in a significant increase in the serum PGA and PGC levels. The 24-h urinary excretion of PGA increased, but that of PGC remained unchanged, and so did the renal clearances of creatinine and pepsinogen A. The renal clearance of pepsinogen C decreased.It was concluded that omeprazole did not affect gastric pepsin output, but, due to the decreased volume output, the concentration of pepsin in the gastric secretion was increased. Omeprazole increased the serum levels of pepsinogen A and C because more pepsinogen was released into the systemic circulation. This might be due to greater back-diffusion of pepsinogen from the gastric mucosa into the systemic circulation as a result of the higher pepsinogen concentration in gastric secretion.     

The effect of hexamethonium on gastric acid secretion in the conscious rat

Evidence against a role for histamine in pentagastrin-stimulated acid secretion has been obtained previously using hexamethonium in gastric fistula rats. This possibility has been re-examined in conscious rats provided with gastric fistulae or Heidenhain pouches. Hexamethonium (20 mg/kg s.c.) inhibited basal acid secretion and acid secretion stimulated by histamine and pentagastrin in gastric fistula rats. The same dose of hexamethonium failed to produce a significant inhibition of acid secretion stimulated by bethanechol, pentagastrin or histamine in the presence of a low dose of bethanechol in Heidenhain pouch rats. These results provide no evidence to oppose the view that pentagastrin-stimulated acid secretion in the rat is mediated at least in part through the mobilization of gastric mucosal histamine. The inhibition of secretagogue induced acid secretion in the gastric fistula rat is mainly the result of a reduction in the basal acid output.