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

By mobilizing histamine in response to gastrin, the ECL cells in the oxyntic mucosa play a key role in the control of the parietal cells and hence of 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 associated with suppressed ECL‐cell histamine secretion. A microdialysis probe was implanted in the submucosa of the ventral aspect of the acid‐producing part of the stomach (32 rats). Three days later, ECL‐cell histamine mobilization was monitored 2 h before and 4 h after the start of intravenous infusion of gastrin (5 nmol kg −1  h −1 ). The rats were either conscious or anaesthetized. Four commonly used anaesthetic agents were given 1 h before the start of the experiments by intraperitoneal injection: chloral hydrate (300 mg kg −1 ), pentobarbitone (40 mg kg −1 ), urethane (1.5 g kg −1 ) and a mixture of fluanisone/fentanyl/midazolam (15/0.5/7.5 mg kg −1 ). In a parallel series of experiments, basal‐ and gastrin‐induced acid secretion was monitored in six conscious and 25 anaesthetized (see above) chronic gastric fistula rats. All anaesthetic agents lowered gastrin‐stimulated acid secretion; also the basal acid output was reduced (fluanisone/fentanyl/midazolam was an exception). Anaesthesia reduced gastrin‐stimulated but not basal histamine release by 55–80%. The reduction in gastrin‐induced acid response (70–95%) was strongly correlated to the reduction in gastrin‐induced histamine mobilization. The correlation is in line with the view that the reduced acid response to gastrin reflects impaired histamine mobilization. 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 exception of urethane, they inhibited gastrin‐evoked histamine secretion dose‐dependently, indicating a direct effect on the ECL cells. Anaesthetized rats are widely used to study acid secretion and ECL‐cell histamine 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 acting in a direct manner.British Journal of Pharmacology (2000) 130 , 725–730; doi: 10.1038/sj.bjp.0703347