Effects of drugs acting on Cl(-)-HCO3- and Na(+)-H+ exchangers on acid secretion in the rat gastric mucosa sheet preparation.
The effects of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of the Cl(-)-HCO3- exchanger, and amiloride, an inhibitor of the Na(+)-H+ exchanger, on gastric acid secretion under basal conditions and after stimulation with bethanechol or dibutyryl cyclic AMP were studied in rat gastric mucosa sheet preparation. DIDS inhibited bethanechol-induced acid secretion in a dose-dependent manner, but amiloride had no effect. The stimulation of acid secretion by dibutyryl cyclic AMP plus 3-isobutyl-1-methylxanthine was also inhibited by DIDs, but not by amiloride. DIDS did not reduce basal acid secretion, and neither did amiloride. These results suggest that the Cl(-)-HCO3-exchanger in the basolateral membrane of the parietal cell plays an important role in stimulated gastric acid secretion and that the Na(+)-H+ exchanger is less important. In addition, these data show that DIDS inhibits stimulated gastric acid secretion irrespective of the secretagogue, but not basal gastric acid secretion.
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; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003994:Bucladesine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D027963:Chloride-Bicarbonate Antiporters; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D017136:Ion Transport / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017923:Sodium-Hydrogen Exchangers
D001626:Bethanechol Compounds; D002352:Carrier Proteins; D027963:Chloride-Bicarbonate Antiporters; D008565:Membrane Proteins; D017923:Sodium-Hydrogen Exchangers; D018723:Bethanechol; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D003994:Bucladesine; D000584:Amiloride; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid