Alimentary pharmacology & therapeutics · 2000
Gastric acid secretion in cyclooxygenase-1 deficient mice.
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Borrelli F, Welsh N J, Sigthorsson G, Simpson R, Palizban A, Bjarnason I, Tavares I A
Аннотация
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 deficient mutant mice did not develop spontaneous gastric pathology and appear less sensitive to indomethacin-induced gastric damage.
AIM: To investigate gastric acid secretion in cyclooxygenase-1 deficient mutant mice.
METHODS: The basal and histamine or isobutyl methylxanthine-stimulated acid secretion in stomachs of cyclooxygenase-1 deficient homozygous mice and the effect of indomethacin was compared with that of heterozygous and wild-type mice using isolated lumen perfused mouse stomachs, in organ baths, monitored by pH-electrodes.
RESULTS: There was no significant difference in the basal or histamine stimulated gastric acid secretion between wild-type or heterozygous or homozygous mice. However, isobutyl methylxanthine was more potent in the cyclooxygenase-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 involvement in cyclooxygenase-1 deficient mice. The finding that basal and histamine-stimulated gastric acid secretion was similar in the cyclooxygenase-1 deficient, compared to wild-type mice is consistent with the lack of spontaneous gastric pathology in the cyclooxygenase-1 deficient mice.
AIM: To investigate gastric acid secretion in cyclooxygenase-1 deficient mutant mice.
METHODS: The basal and histamine or isobutyl methylxanthine-stimulated acid secretion in stomachs of cyclooxygenase-1 deficient homozygous mice and the effect of indomethacin was compared with that of heterozygous and wild-type mice using isolated lumen perfused mouse stomachs, in organ baths, monitored by pH-electrodes.
RESULTS: There was no significant difference in the basal or histamine stimulated gastric acid secretion between wild-type or heterozygous or homozygous mice. However, isobutyl methylxanthine was more potent in the cyclooxygenase-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 involvement in cyclooxygenase-1 deficient mice. The finding that basal and histamine-stimulated gastric acid secretion was similar in the cyclooxygenase-1 deficient, compared to wild-type mice is consistent with the lack of spontaneous gastric pathology in the cyclooxygenase-1 deficient mice.
Предметные рубрики MeSH
1-Methyl-3-isobutylxanthineAlgorithmsAnimalsCyclooxygenase 1Cyclooxygenase InhibitorsGastric AcidGenotypeHistamineHydrogen-Ion ConcentrationIn Vitro TechniquesIndomethacinIsoenzymesMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutPerfusionPhosphodiesterase InhibitorsProstaglandin-Endoperoxide SynthasesProstaglandins