Wallmark B, Jaresten B M, Larsson H, Ryberg B, Brändström A, Fellenius E
Am J Physiol. 1983 Jul;245(1):G64-71. doi: 10.1152/ajpgi.1983.245.1.G64.
The action of the substituted benzimidazole omeprazole (H 168/68) was studied in three different in vitro preparations: the isolated guinea pig gastric mucosa, isolated intact and permeable rabbit gastric glands, and hog fundic microsomal membrane vesicles containing H+-K+-ATPase. The effects of omeprazole were compared with those of cimetidine and thiocyanate (SCN-). Under all the conditions studied, cimetidine only counteracted histamine-induced acid secretion, consonant with its H2-receptor antagonism. In contrast, omeprazole and SCN- were found not only to inhibit histamine-induced secretion but also basal acid formation and acid formation induced by dibutyryl cAMP and a high cell medium concentration of K+. Moreover, acid production induced by ATP in permeable gastric glands was antagonized by omeprazole and SCN-, whereas cimetidine was without effect. The interaction pattern of omeprazole and SCN- was differentiated by studies using the weak base antipyrine in the isolated mucosal preparation, where it was found that antipyrine could reverse the inhibition induced by SCN- but not that of omeprazole. Furthermore, omeprazole was found to inhibit the isolated H+-K+-ATPase, whereas cimetidine or SCN- was without effect. In the isolated mucosal preparation omeprazole caused an increase in K+ secretion rates in parallel with the inhibition of acid formation. This was in contrast to what was observed for cimetidine and SCN-, which exhibited no such increased K+ secretion. The results obtained from intact mucosa and isolated glands are in agreement with the ability of omeprazole to inhibit the isolated H+-K+-ATPase and thus provide evidence of a novel mechanism of action for this inhibitor.
在三种不同的体外制剂中研究了取代苯并咪唑奥美拉唑（H 168/68）的作用：分离的豚鼠胃黏膜、分离的完整且可渗透的兔胃腺以及含有H⁺-K⁺-ATP酶的猪胃底微粒体膜囊泡。将奥美拉唑的作用与西咪替丁和硫氰酸盐（SCN⁻）的作用进行了比较。在所有研究条件下，西咪替丁仅抵消组胺诱导的胃酸分泌，这与其H₂受体拮抗作用一致。相比之下，发现奥美拉唑和SCN⁻不仅抑制组胺诱导的分泌，还抑制基础胃酸形成以及由二丁酰环磷腺苷和高细胞培养基浓度的钾诱导的胃酸形成。此外，奥美拉唑和SCN⁻拮抗了可渗透胃腺中由ATP诱导的产酸，而西咪替丁则无此作用。在分离的黏膜制剂中使用弱碱安替比林进行研究，区分了奥美拉唑和SCN⁻的相互作用模式，发现安替比林可逆转SCN⁻诱导的抑制作用，但不能逆转奥美拉唑的抑制作用。此外，发现奥美拉唑抑制分离的H⁺-K⁺-ATP酶，而西咪替丁或SCN⁻则无此作用。在分离的黏膜制剂中，奥美拉唑导致钾分泌速率增加，同时抑制胃酸形成。这与西咪替丁和SCN⁻的情况相反，它们未表现出这种钾分泌增加。从完整黏膜和分离腺体制备中获得的结果与奥美拉唑抑制分离的H⁺-K⁺-ATP酶的能力一致，从而为该抑制剂的新作用机制提供了证据。
