Journal
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Volume 291, Issue 5, Pages G838-G843Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00120.2006
Keywords
potassium competitive acid blockers; gastric acid secretion; pH measurements; gastroesophageal reflux disease
Categories
Funding
- NIDDK NIH HHS [DK-007259-26, DK-07017-29] Funding Source: Medline
- PHS HHS [D-K50230] Funding Source: Medline
Ask authors/readers for more resources
The gastric H+, K+-ATPase of the parietal cell is responsible for acid secretion in the stomach and is the main target in the pharmacological treatment of acid-related diseases. Omeprazole and other benzimidazole drugs, although having delayed efficacy if taken orally, have high success rates in the treatment of peptic ulcer disease. Potassium competitive acid blockers (P-CAB) compete with K+ for binding to the H+, K+-ATPase and thereby they inhibit acid secretion. In this study, the in vitro properties of AZD0865, a reversible H+, K+-ATPase inhibitor of gastric acid secretion, are described. We used a digital-imaging system and the pH sensitive dye BCECF to observe proton efflux from hand-dissected rat gastric glands. Glands were stimulated with histamine (100 mu M) and exposed to a bicarbonate- and Na+-free perfusate to induce an acid load. H+, K+-ATPase inhibition was determined by calculating pH(i) recovery (dpH/dT) in the presence of omeprazole (10-200 mu M) or AZD0865 (0.01-100 mu M). The efficacies of both drugs were compared. Our data show that acid secretion is inhibited by both the proton pump inhibitor omeprazole and the P-CAB AZD0865. Complete inhibition of acid secretion by AZD0865 had a rapid onset of activation, was reversible, and occurred at a 100-fold lower dose than omeprazole (1 mu M AZD0865 vs. 100 mu M omeprazole). This study demonstrates that AZD0865 is a potent, fast-acting inhibitor of gastric acid secretion, effective at lower concentrations than drugs of the benzimidazole class. Therefore, these data strongly suggest that AZD0865 has great potential as a fast-acting, low-dose inhibitor of acid secretion.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available