Horie S, Yano S, Watanabe K
Department of Drug Evaluation and Toxicological Sciences, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
J Pharmacol Exp Ther. 1993 Jun;265(3):1313-8.
The mode of action of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of the Cl(-)-HCO3- exchanger, on gastric acid secretion has been studied in vitro and in vivo. In the mouse isolated whole stomach preparation, DIDS (100 microM-1 mM) inhibited gastric acid secretion induced by histamine or bethanechol in a concentration-dependent fashion. On the other hand, DIDS, at a concentration enough to reduce the stimulated acid secretion, did not inhibit basal acid secretion in the resting preparation. In the perfused stomach of urethane-anesthetized rats, DIDS (1-10 mg/kg i.v.) inhibited gastric acid secretion stimulated by histamine, bethanechol or tetragastrin, whereas DIDS did not inhibit basal acid secretion. In pylorus-ligated rats, DIDS (3-30 mg/kg) administered intraduodenally also inhibited gastric acid output as well as gastric juice volume when administered immediately after ligation. When injected 6 h before ligation, DIDS inhibited the gastric acid secretion. However, this potency was weak in comparison with that observed when DIDS was administered immediately after ligation. These results demonstrate that DIDS can inhibit stimulated gastric acid secretion in vitro and in vivo, probably through its inhibitory effect on the Cl(-)-HCO3- exchanger.
4,4'-二异硫氰基芪-2,2'-二磺酸(DIDS)是一种Cl(-)-HCO3-交换体抑制剂,其对胃酸分泌的作用机制已在体外和体内进行了研究。在小鼠离体全胃制备实验中,DIDS(100微摩尔/升至1毫摩尔/升)以浓度依赖性方式抑制组胺或氨甲酰甲胆碱诱导的胃酸分泌。另一方面,在足以降低刺激胃酸分泌的浓度下,DIDS并未抑制静息状态下的基础胃酸分泌。在氨基甲酸乙酯麻醉大鼠的灌流胃实验中,DIDS(静脉注射1至10毫克/千克)抑制组胺、氨甲酰甲胆碱或四肽胃泌素刺激的胃酸分泌,而DIDS不抑制基础胃酸分泌。在幽门结扎大鼠中,十二指肠内给予DIDS(3至30毫克/千克),在结扎后立即给药时,也抑制胃酸分泌以及胃液量。在结扎前6小时注射时,DIDS抑制胃酸分泌。然而,与结扎后立即给予DIDS时观察到的效力相比,这种效力较弱。这些结果表明,DIDS可能通过对Cl(-)-HCO3-交换体的抑制作用,在体外和体内抑制刺激的胃酸分泌。