Effects of anaesthetic agents on gastrin-stimulated and histamine-stimulated gastric acid secretion in the totally isolated vascularly perfused rat stomach.
ABSTRACT Anaesthetic agents affect gastric acid secretion, but the mechanisms behind this action have not been fully evaluated. The enterochromaffin-like (ECL) cell plays a key role in the regulation of gastric acid secretion, and anaesthetic agents have recently been described as inhibiting histamine release from the ECL cell. The present study examines the effect of anaesthetic agents on the ECL cell and on parietal cell functions.
Different concentrations of urethane, pentobarbital and a mixture of fluanisone/fantanyl/midazolam (FFM) were examined for the effect on gastrin-stimulated histamine release and acid secretion and on histamine-stimulated acid secretion in the totally isolated vascularly perfused rat stomach. The luminal acid output and histamine concentrations in venous effluents were measured by titration and radioimmunoassay, respectively.
Pentobarbital caused an inhibition on both histamine release and acid output in gastrin-stimulated stomachs in a concentration-dependent way. The mixture of FFM at higher concentrations inhibited histamine release from the ECL cell and luminal H+ output in gastrin-stimulated acid secretion. Urethane exerted a slight inhibitory effect on histamine release only at the lowest concentration. Pentobarbital also reduced histamine-stimulated gastric acid secretion, while the mixture of FFM did not.
pentobarbital inhibits acid secretion both by reducing ECL cell histamine release and parietal cell H+ secretion, whereas FFM inhibits acid secretion by interaction with the ECL cell only. Urethane also had a slight inhibitory effect on the ECL cell histamine release at the lowest concentration.
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ABSTRACT: To safely manage the hypersecretory state in patients with Zollinger-Ellison syndrome, both upper endoscopy and gastric analysis are required to titrate optimal medical therapy. Conventional gastric analysis requires more than 1 hour to perform and results in significant patient dissatisfaction. In this study, we have validated endoscopic gastric analysis as a novel technique that can effectively replace conventional gastric analysis. In a prospective, cross-over study, 12 patients with Zollinger-Ellison syndrome underwent gastric analysis, first by the conventional method and then by an endoscopic technique performed on the same day. Acid concentration was determined by titration, volume output was recorded, and acid output was calculated using standard methodologies and formulas. Agreement was assessed following the Bland-Altman method. To assess repeatability, both techniques were repeated on the same day in a subset of patients. Excellent agreement was reported between acid output (95% limits of agreement, -1.27 to 1.61 mEq/h) and acid concentration (95% limits of agreement, -0.01 to 0.01 mEq/mL), although poor agreement was observed between volume output measured. Endoscopic gastric analysis showed greater reproducibility regarding acid and volume output measured. We introduce a new, rapid, reproducible, and accurate endoscopic technique to measure acid output in patients with Zollinger-Ellison syndrome who require both annual endoscopy and gastric analysis. The data presented here suggest that endoscopic gastric analysis would be equally effective in determining acid output in other hypersecretory states. Additional analysis of cost effectiveness is needed to evaluate its use as a screening tool in select populations.Clinical Gastroenterology and Hepatology 01/2007; 4(12):1467-73. · 6.65 Impact Factor
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ABSTRACT: The ECL cells in the oxyntic mucosa secrete histamine in response to gastrin, stimulating parietal cells to produce acid. Do they also operate under nervous control? The present study examines histamine mobilization from rat stomach ECL cells in situ in response to acute vagal excitation and to food or gastrin following vagal or sympathetic denervation. Applying the technique of microdialysis, we monitored the release of histamine by radioimmunoassay. Microdialysis probes were placed in the submucosa on either side of the stomach, 3 days before experiments. The rats were awake during microdialysis except when subjected to electrical vagal stimulation. One-sided electrical vagal stimulation raised serum gastrin and mobilized gastric histamine. However, gastrin receptor blockade prevented the histamine mobilization, indicating that circulating gastrin accounts for the response. Vagal excitation by hypoglycaemia (insulin) or pylorus ligation did not mobilize either gastrin or histamine. The histamine response to food was almost abolished by gastrin receptor blockade, and it was halved on the denervated side after unilateral subdiaphragmatic vagotomy. While the histamine response to a near-maximally effective dose of gastrin was unaffected by vagotomy, the response to low gastrin doses was reduced significantly. Abdominal ganglionic sympathectomy failed to affect the histamine response to either food or gastrin. In conclusion, gastrin is responsible for most of the food-evoked mobilization of ECL-cell histamine. The histamine response to electrical vagal stimulation reflects the effect of circulating gastrin rather than a direct action of the vagus on the ECL cells. Vagal denervation was accompanied by an impaired histamine response to food intake, probably reflecting the right-ward shift of the serum gastrin concentration-histamine response curve. The results suggest that the vagus controls the sensitivity of the ECL cells to gastrin.The Journal of Physiology 06/2005; 564(Pt 3):895-905. · 4.38 Impact Factor
Article: Gastric Secretion[show abstract] [hide abstract]
ABSTRACT: Abstract The present study was performed in six asymptomatic patients with a history of resistant duodenal ulcers in whom 24 h intragastric pH, gastric juice pepsin and PGE2 concentrations, as well as serum gastrin concentrations, were measured. We wanted to compare the effects on these parameters of a single night time (q.h.s.) dose of nizatidine 300 mg (N1), nizatidine 300 mg b.i.d. (N2), ranitidine 300 mg q.h.s. (R1) or ranitidine 300 mg b.i.d. (R2) compared with placebo (P). During the night (22.00–08.00 h), all treatments gave a higher mean pH than P, but during the day (08.00–22.00 h) the mean pH was higher than P only for patients administered R2 and N2. Doubling the dose of nizatidine (N2vs N1) or ranitidine (R2vs R1) increased the mean daytime pH, but had no effect on night time pH. The daytime pepsin concentration was unaffected by H2-receptor antagonists, while night time pepsin was lower with R1 and R2, but not with N1 or N2. The night time gastrin concentration was unaffected by H2-receptor antagonists; doubling the dose of the H2-receptor antagonist (R2vs R1 and N2vs N1) increased daytime gastrin concentration. During the night, each treatment increased PGE2 concentration by at least six-fold compared with P. Thus, where it is therapeutically indicated to achieve greater suppression of acid secretion, doubling the total daily dose by dosing with twice daily versus once daily night time nizatidine or ranitidine is efficacious.Journal of Gastroenterology and Hepatology 03/2008; 11(12):1171 - 1176. · 3.33 Impact Factor