INTERACTION OF THE ANTIINFLAMMATORY SELENOORGANIC COMPOUND EBSELEN WITH ACID-SECRETION IN ISOLATED PARIETAL-CELLS AND GASTRIC H+/K+-ATPASE
INTERACTION OF THE ANTIINFLAMMATORY SELENOORGANIC COMPOUND EBSELEN WITH ACID-SECRETION IN ISOLATED PARIETAL-CELLS AND GASTRIC H+/K+-ATPASE
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DOI：
10.1016/0006-2952(90)90229-e
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发表时间：
1990-11-01
影响因子：
5.8
通讯作者：
SEWING, KF
中科院分区：
文献类型：
--
作者：
BEIL, W;STAAR, U;SEWING, KF
研究了抗炎有机硒化合物依布硒啉对胃 H+/K+-ATP 酶、H+/K+-ATP 酶介导的质子转运和部分细胞 HCl 产生的影响。 Ebselen抑制渗漏胃膜中K+刺激的ATP酶活性(IC50：0.15μM)和完整胃膜囊泡中H+/K+-ATP酶介导的质子转运(IC50：0.7μM)。在分离和富集的豚鼠壁细胞中组胺和二丁酰cAMP刺激的HCl产生被抑制，IC50值为12μM。硫醇二硫赤藓糖醇和核苷酸 ATP 可防止 H+/K+-ATP 酶失活，并且发现二硫赤藓糖醇可恢复已受抑制的酶活性和 ATP 酶介导的 H+ 转运。此外，二硫赤藓糖醇可以防止依布硒啉诱导的壁细胞制剂中 HCl 产生的抑制。结论是，依布硒啉通过干扰胃质子泵（H+/K+-ATP酶）的SH基团来抑制壁细胞的酸分泌。因此，依布硒啉可被视为一种抗炎药，其体外抗分泌特性已得到证实。
The effects of the anti-inflammatory seleno-organic compound ebselen on gastric H+/K+-ATPase, H+/K+-ATPase-mediated proton transport and on partietal cell HCl production was studied. Ebselen inhibited K+-stimulated ATPase activity in leaky gastric membranes (IC50:0.15 .mu.M) and H+/K+-ATPase-mediated proton transport in intact gastric membrane vesicles (IC50:0.7 .mu.M). Histamine-and dibutyryl-cAMP-stimulated HCl production in isolated and enriched guinea-pig parietal cells was inhibited with an IC50 value of 12 .mu.M. The mercaptan dithioeythritol and the nucleotide ATP prevents the H+/K+-ATPase against inactivation and dithioerythritol was found to restore already inhibited enzyme activity and ATPase mediated H+ transport. Furthermore, dithioerthritol could prevent ebselen-induced inhibition of HCl production in the parietal cell preparation. It is concluded that ebselen inhibits acid secretion in the parietal cell by interference with SH groups of the gastric proton pump, the H+/K+-ATPase. Therefore ebselen can be regarded as an anti-inflammatory drug for which in vitro anti-secretory properties can be demonstrated.