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.
Norlén
P
P
Department of Pharmacology, Institute of Physiological Sciences, University of Lund, Sölvegatan 10, Lund, Sweden.
Kitano
M
M
Lindström
E
E
Håkanson
R
R
D000704:Analysis of Variance; D000758:Anesthesia; D000777:Anesthetics / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D002090:Butyrophenones / Q000494:pharmacology; D002478:Cells, Cultured; D002697:Chloral Hydrate / Q000494:pharmacology; D003243:Consciousness; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D005747:Gastric Fistula; D005753:Gastric Mucosa / Q000378:metabolism; D005755:Gastrins / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D007262:Infusions, Intravenous; D008297:Male; D017551:Microdialysis; D008874:Midazolam / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000166:cytology / Q000187:drug effects*; D014520:Urethane / Q000494:pharmacology
D000777:Anesthetics; D018686:Anesthetics, Intravenous; D002090:Butyrophenones; D005755:Gastrins; C005014:fluanisone; D014520:Urethane; D002697:Chloral Hydrate; D010424:Pentobarbital; D008874:Midazolam; D005283:Fentanyl