Inhibition of gastric acid secretion in vivo and in vitro by an inhibitor of Cl(-)-HCO3- exchanger, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid.
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.
Department of Drug Evaluation and Toxicological Sciences, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
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D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D027963:Chloride-Bicarbonate Antiporters; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D051379:Mice; D009853:Omeprazole / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects*
D002352:Carrier Proteins; D027963:Chloride-Bicarbonate Antiporters; D008565:Membrane Proteins; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D009853:Omeprazole; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid