Fimmel C J, Berger M M, Blum A L
Am J Physiol. 1984 Sep;247(3 Pt 1):G240-7. doi: 10.1152/ajpgi.1984.247.3.G240.
The effect of omeprazole, an inhibitor of the parietal cell H+-K+-ATPase, on pepsin and acid secretion was studied in an in vitro perfused whole mouse stomach model. Omeprazole inhibited basal and dibutyryl cAMP (DBcAMP)- and histamine-stimulated acid secretion in a dose-dependent fashion with a maximally effective dose of 10(-4) M. At the same time, omeprazole induced a dose-dependent increase of unstimulated pepsin release. This increase was not affected by pretreatment with 10(-3) M atropine or 10(-4) M cimetidine. It was, however, inhibited by preincubation with 10(-4) M carbonyl cyanide m-chlorophenylhydrazone (CCCP). Pepsin secretion after maximally effective doses of histamine or DBcAMP was not affected by 10(-4) M omeprazole. In a concentration of 10(-5) M, the effect of omeprazole was additive to the effect of submaximal concentrations of carbachol and histamine. NaSCN and imidazole mimicked the effect of omeprazole on acid secretion, but pepsin release was only stimulated with 10(-2) M imidazole. Another weak base, benzylamine, stimulated acid and pepsin in parallel. Luminal perfusion with solutions of high K+ concentration did not enhance basal pepsin release. The dissociated response of acid and pepsin secretion indicates that omeprazole does not act selectively on the parietal cell. The stimulation of pepsin secretion might be related to the weak base properties of the compound.
在体外灌注的全小鼠胃模型中，研究了壁细胞H⁺-K⁺-ATP酶抑制剂奥美拉唑对胃蛋白酶和胃酸分泌的影响。奥美拉唑以剂量依赖方式抑制基础胃酸分泌以及二丁酰环磷腺苷（DBcAMP）和组胺刺激的胃酸分泌，最大有效剂量为10⁻⁴M。同时，奥美拉唑诱导未刺激状态下胃蛋白酶释放呈剂量依赖性增加。这种增加不受10⁻³M阿托品或10⁻⁴M西咪替丁预处理的影响。然而，用10⁻⁴M羰基氰化物间氯苯腙（CCCP）预孵育可抑制该增加。最大有效剂量的组胺或DBcAMP刺激后的胃蛋白酶分泌不受10⁻⁴M奥美拉唑的影响。在10⁻⁵M浓度下，奥美拉唑的作用与次最大浓度的卡巴胆碱和组胺的作用相加。硫氰酸钠和咪唑模拟了奥美拉唑对胃酸分泌的作用，但仅用10⁻²M咪唑刺激胃蛋白酶释放。另一种弱碱苄胺同时刺激胃酸和胃蛋白酶分泌。用高钾浓度溶液进行腔内灌注未增强基础胃蛋白酶释放。胃酸和胃蛋白酶分泌的解离反应表明奥美拉唑并非选择性地作用于壁细胞。胃蛋白酶分泌的刺激可能与该化合物的弱碱性质有关。
