Anaesthetic agents inhibit gastrin-stimulated but not basal histamine release from rat stomach ECL cells

1 By mobilizing histamine in response to gastrin, the ECL cells in the oxyn tic mucosa play a key role in the control of the parietal cells and hence o f gastric acid secretion. General anaesthesia suppresses basal and gastrin- and histamine-stimulated acid secretion. The present study examines if the effect of anaesthesia on basal and gastrin-stimulated acid secretion is as sociated with suppressed ECL-cell histamine secretion. 2 A microdialysis probe was implanted in the submucosa of the ventral aspec t of the acid-producing part of the stomach (32 rats). Three days later, EC L-cell histamine mobilization was monitored 2 h before and 4 h after the st art of intravenous infusion of gastrin (5 nmol kg(-1) h(-1)). The rats were either conscious or anaesthetized. Four commonly used anaesthetic agents w ere given 1 h before the start of the experiments by intraperitoneal inject ion: chloral hydrate (300 mg kg(-1)), pentobarbitone (40 mg kg(-1)), uretha ne (1.5 g kg(-1)) and a mixture of fluanisone/fentanyl/midazolam (15/0.5/7. 5 mg kg(-1)). 3 In a parallel series of experiments, basal- and gastrin-induced acid secr etion was monitored in six conscious and 35 anaesthetized (see above) chron ic gastric fistula rats. All anaesthetic agents lowered gastrin-stimulated acid secretion; also the basal acid output was reduced (fluanisone/fentanyl / midazolam was an exception). 4 Anaesthesia reduced gastrin-stimulated but not basal histamine release by 55-80%. The reduction in gastrin-induced acid response (70-95%) was strong ly correlated to the reduction in gastrin-induced histamine mobilization. T he correlation is in line with the view that the reduced acid response to g astrin reflects impaired histamine mobilization. 5 Rat stomach ECL cells were purified by counter-flow elutriation. Gastrin- evoked histamine mobilization from the isolated ECL cells was determined in the absence or presence of anaesthetic agents in the medium. With the exce ption of urethane, they inhibited gastrin-evoked histamine secretion dose-d ependently, indicating a direct effect on the ECL cells. 6 Anaesthetized rats are widely used to study acid secretion and ECL-cell h istamine release. The present results illustrate the short-comings of such an approach in that a number of anaesthetic agents were found to impair not only acid secretion but also the secretion of ECL-cell histamine some acti ng in a direct manner.