scholarly journals Omeprazole Inhibits Acetylsalicylic Acid-Modified Histamine Stimulation of Acid Secretion in Rabbit Gastric Glands

1994 ◽  
Vol 8 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Daniel T Brosseuk ◽  
Iain GM Cleator ◽  
Andrew J Rae ◽  
Gilbert Wankling
Keyword(s):  
Acetylsalicylic Acid ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Mucosal Injury ◽  
Gastric Glands ◽  
Histamine Stimulation ◽  
Inhibited Acid ◽  
Stimulation Of

The effects of misoprostol and omeprazole on basal-, histamine- and acetylsalicylic acid (ASA)-induced gastric acid secretion by isolated rabbit gastric glands were studied. The authors found that ASA at a concentration of 2.4×10-3 M significantly inhibited acid secretion in the isolated gastric glands to 65% of basal levels, and that ASA at a concentration of 2.4×l0-2 M significantly inhibited the histamine stimulation of acid secretion to 78% of maximal. Misoprostol inhibited acid secretion to 76% of basal acid secretion, while omeprazole inhibited secretion to 58% of basal values. Misoprostol inhibited the ASA-modified histamine stimulation to 82% of maximal stimulation. In contrast, omeprazole was able to inhibit the ASA-modified histamine stimulation to 48% of maximal. This omeprazole inhibition of secretagogue-induced acid production reduced acid secretion to levels below basal secretion, indicating that neither histamine nor ASA (at the concentrations used), alone or in combination, had any stimulatory effect in the presence of omeprazole. Misoprostol is the recommended drug of choice for prevention and treatment of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal mucosal injury. In vitro results suggest that omeprazole appears to treat this condition more effectively if gastric acid secretion is a necessary prerequisite for NSAID-induced mucosal injury.

Characteristics of the K+-competitive H+,K+-ATPase inhibitor AZD0865 in isolated rat gastric glands

2006 ◽  
Vol 291 (5) ◽  
pp. G838-G843 ◽  
Author(s):  
P. Kirchhoff ◽  
K. Andersson ◽  
T. Socrates ◽  
S. Sidani ◽  
O. Kosiek ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Imaging System ◽  
Success Rates ◽  
Atpase Inhibitor ◽  
Gastric Glands ◽  
Ulcer Disease ◽  
Fast Acting

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 μM) and exposed to a bicarbonate- and Na+-free perfusate to induce an acid load. H+,K+-ATPase inhibition was determined by calculating pHi recovery (dpH/dT) in the presence of omeprazole (10–200 μM) or AZD0865 (0.01–100 μM). 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 μM AZD0865 vs. 100 μM 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.

Nitric oxide inhibits gastric acid secretion by increasing intraparietal cell levels of cGMP in isolated human gastric glands

2005 ◽  
Vol 289 (6) ◽  
pp. G1061-G1066 ◽  
Author(s):  
Anna Berg ◽  
Stefan Redéen ◽  
Magnus Grenegård ◽  
Ann-Charlott Ericson ◽  
Sven Erik Sjöstrand
Keyword(s):  
Nitric Oxide ◽  
Gastric Mucosa ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Enzymatic Digestion ◽  
Human Gastric Mucosa ◽  
Gastric Glands ◽  
Oxyntic Mucosa ◽  
No Donor

We have previously identified cells containing the enzyme nitric oxide (NO) synthase (NOS) in the human gastric mucosa. Moreover, we have demonstrated that endogenous and exogenous NO has been shown to decrease histamine-stimulated acid secretion in isolated human gastric glands. The present investigation aimed to further determine whether this action of NO was mediated by the activation of guanylyl cyclase (GC) and subsequent production of cGMP. Isolated gastric glands were obtained after enzymatic digestion of biopsies taken from the oxyntic mucosa of healthy volunteers. Acid secretion was assessed by measuring [14C]aminopyrine accumulation, and the concentration of cGMP was determined by radioimmunoassay. In addition, immunohistochemistry was used to examine the localization of cGMP in mucosal preparations after stimulation with the NO donor S-nitroso- N-acetylpenicillamine (SNAP). SNAP (0.1 mM) was shown to decrease acid secretion stimulated by histamine (50 μM); this effect was accompanied by an increase in cGMP production, which was histologically localized to parietal cells. The membrane-permeable cGMP analog dibuturyl-cGMP (db-cGMP; 0.1–1 mM) dose dependently inhibited acid secretion. Additionally, the effect of SNAP was prevented by preincubating the glands with the GC inhibitor 4 H-8-bromo-1,2,4-oxadiazolo[3,4-d]benz[b][1,4]oxazin-1-one (10 μM). We therefore suggest that NO in the human gastric mucosa is of physiological importance in regulating acid secretion. Furthermore, the results show that NO-induced inhibition of gastric acid secretion is a cGMP-dependent mechanism in the parietal cell involving the activation of GC.

Effect of caffeic acid phenethyl ester on gastric acid secretion in vitro

2005 ◽  
Vol 521 (1-3) ◽  
pp. 139-143 ◽  
Author(s):  
Francesca Borrelli ◽  
Inmaculada Posadas ◽  
Raffaele Capasso ◽  
Gabriella Aviello ◽  
Valeria Ascione ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Caffeic Acid ◽  
Caffeic Acid Phenethyl Ester
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