Gastric acid secretion in cyclooxygenase-1 deficient mice

Background: Constitutive cyclooxygenase-1 enzyme synthesizes prostaglandins which are thought to play an important role in the functional integrity of the stomach gastric mucosa. Recently, it was shown that cyclooxygenase-1 d eficient mutant mice did not develop spontaneous gastric pathology and appe ar less sensitive to indomethacin-induced gastric damage. Aim: To investigate gastric acid secretion in cyclooxygenase-1 deficient mu tant mice. Methods: The basal and histamine or isobutyl methylxanthine-stimulated acid secretion in stomachs of cyclooxygenase-1 deficient homozygous mice and th e effect of indomethacin was compared with that of heterozygous and wild-ty pe mice using isolated lumen perfused mouse stomachs, in organ baths, monit ored by pH-electrodes. Results: There was no significant difference in the basal or histamine stim ulated gastric acid secretion between wild-type or heterozygous or homozygo us mice. However, isobutyl methylxanthine was more potent in the cyclooxyge nase-1 deficient and heterozygous mice than in wild-type mice. Indomethacin , at concentrations below 1 mM, had no effect on either basal or histamine stimulated acid secretion in any of the mice populations. Conclusion: Gastric acid secretion is maintained without prostaglandin invo lvement in cyclooxygenase-1 deficient mice. The finding that basal and hist amine-stimulated gastric acid secretion was similar in the cyclooxygenase-1 deficient, compared to wild-type mice is consistent with the lack of spont aneous gastric pathology in the cyclooxygenase-1 deficient mice.