Mobilization of rat stomach ECL-cell histamine in response to short- or long-term treatment with omeprazole and/or YF 476 studied by gastric submucosal microdialysis in conscious rats

1 Mobilization of histamine from the ECL cells was monitored by gastric sub mucosal microdialysis in conscious rats. The ECL cells are known to operate under gastrin control and the purpose of the present study was to examine their in situ response to short-term (12 h) as well as long-term (28 days) hypergastrinaemia, induced by treatment with the proton pump inhibitor omep razole. 2 Hypergastrinaemia promptly raised the histamine concentration in the micr odialysate. The effect was prevented by CCK2 receptor blockade (YF476). On day 7 of omeprazole treatment the microdialysate histamine concentration re ached a peak, five times higher than before treatment. Subsequently (14 and 28 days), less histamine was mobilized. 3 Gastrin infusion (4 h) raised the microdialysate histamine concentration in a dose-dependent manner in fasted rats and freely fed rats and in rats t reated with omeprazole for a week. However, while fasted and fed rats respo nded to low doses of gastrin, the omeprazole-treated rats required large do ses of gastrin to respond. 4 When the amount of histamine mobilized was related to the serum gastrin c oncentration the following EC50 values could be calculated: fasted rats 2.3 x 10-(10) M, freely fed rats 2.5 x 10-(10) M, omeprazole-treated rats 8.7 x 10(-10) M. The maximal histamine responses in the three groups were 18.4 pmol 4 h(-1)+/-0.8, 21.9 pmol 4 h(-1)+/-1.2 and 68.0 pmol 4 h(-1)+/-3.5, re spectively. 5 The results suggest that ECL cells, exposed to a high gastrin concentrati on for a week, respond with a shift in the receptor-ligand binding affinity from high to low. Apparently, CCK2 receptors of the ECL cells are subject to dynamic changes with respect to ligand-binding affinity.