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.
Horie
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S
Department of Drug Evaluation and Toxicological Sciences, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Yano
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S
Watanabe
K
K
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